To investigate the expression characteristics, prognostic significance, and the association of hephaestin (HEPH) with cell migration, invasion, and epithelial-mesenchymal transition (EMT) in pancreatic cancer.

Expression differences of HEPH in pan-cancer and pancreatic cancer tissues were analyzed through public databases, with validation of HEPH expression levels in clinical samples. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic value of HEPH. Gene set enrichment analysis (GSEA) was performed by grouping samples based on HEPH expression levels and using gene expression fold change as the ranking metric to identify significantly enriched biological pathways. Stable HEPH knockdown pancreatic cancer cell lines, PANC-1 and SW1990, were established. Cells infected with pLKO.1-Puro empty vector lentivirus were designated as the scramble group (negative control), and cells infected with shHEPH lentivirus were designated as shHEPH-1, shHEPH-2, and shHEPH-3 knockdown groups. Knockdown efficiency was verified by RT-qPCR and Western blot. The effects of HEPH on cell migration and invasion were assessed using scratch and Transwell assays. Expression changes of EMT-related markers (E-cadherin, N-cadherin, and Vimentin) were measured. Comparisons between two groups were performed using independent samples t-test. Comparisons among multiple groups were analyzed by one-way ANOVA followed by Dunnett's t-test for pairwise comparisons. Survival analysis was conducted using univariate Cox regression to calculate hazard ratios and 95% confidence intervals, and Kaplan-Meier survival curves were plotted.

HEPH was highly expressed in pancreatic cancer tissues, and high expression was associated with shorter overall survival in patients (HR = 1.55, P = 0.038). ROC analysis showed that the AUCs of HEPH for 3-year and 5-year overall survival of pancreatic cancer patients were 0.638 and 0.678, respectively. Immunohistochemical and paired tissue analyses further confirmed the high expression of HEPH in pancreatic cancer tissues. GSEA revealed that the EMT pathway was significantly enriched in the high HEPH expression group (NES = 3.000, P < 0.001). Compared with the scramble group, knockdown of HEPH reduced the migration (PANC-1: 148.70 ± 19.30 vs 314.30 ± 55.97; SW1990: 175.00 ± 24.58 vs 425.00 ± 26.51) and invasion (PANC-1: 97.67 ± 15.57 vs 227.70 ± 21.73; SW1990: 90.67 ± 11.93 vs 321.30 ± 34.70) abilities of PANC-1 and SW1990 cells (all P < 0.01). Compared to the control group, the HEPH knockdown group showed increased E-cadherin expression (PANC-1: 3.07 ± 0.48 vs 1.00 ± 0.05; SW1990: 2.58 ± 0.41 vs 1.00 ± 0.02; all P < 0.000 1) and decreased N-cadherin (PANC-1: 0.33 ± 0.06 vs 1.01 ± 0.05; SW1990: 0.44 ± 0.08 vs 1.00 ± 0.05; all P < 0.01) and Vimentin (PANC-1: 0.36 ± 0.06 vs 1.00 ± 0.02; SW1990: 0.39 ± 0.06 vs 0.99 ± 0.02; all P < 0.01) expression.

HEPH is highly expressed in pancreatic cancer and is associated with poor prognosis. Knockdown of HEPH suppresses migration and invasion of pancreatic cancer cells, accompanied by altered expression of EMT markers, suggesting that high HEPH expression is correlated with EMT activation and enhanced migratory/invasive capabilities. This suggests that HEPH may serve as a potential biomarker for prognosis and therapeutic intervention in pancreatic cancer.

To explore the effects and duration of adipose-derived mesenchymal stem cells (ADSCs) on cartilage injury and inflammatory response in knee osteoarthritis (KOA) rats.

Forty-five male SD rats were divided into the blank group, model group and treatment group randomly. Fourteen days after the KOA model establishment, the rats in the treatment group were injected with 1×10⁶ ADSCs/50 μL into the articular cavity while rats in the blank group and the KOA model group were injected with the same volume of normal saline once a week for four consecutive injections. The rats were observed at 4 weeks, 8 weeks and 12 weeks (n = 5) after the first injection. Independent blank group, model group and treatment group were set up at each observation time point. The mechanical pain threshold and thermal pain threshold of rats in each group were monitored and recorded. The degree of cartilage degeneration was observed by micro CT, HE-staining, Safranine O-fast green staining and Alcian blue staining. The protein expressions of collagen Ⅱ (COL2A1) and aggrecan (ACAN) were detected by immunohistochemistry. The expression levels of inflammatory factors IL-1β and TNF-α in articular cavity lavage fluid were detected by ELISA. Two-way factorial design ANOVA was used to analyze the main effect of group and observation time for all measurement data, and Bonferroni post-test was used for pairwise comparison.

The main effects of group in mechanical pain threshold, bone volume fraction, trabecular bone separation, Mankin score, OARSI score, COL2A1 and IL-1β in each group were statistically significant (all P < 0.05), while there was no significant difference in the main effects of time (all P > 0.05); The main effects of group and time were significant in terms of thermal pain threshold, trabecular thickness, trabecular number, ACAN and TNF-α (all P < 0.05). Compared with the blank group, the mechanical pain threshold, the thermal pain threshold, bone volume fraction, trabecular thickness and trabecular number [4 weeks: (0.92 ± 0.02) vs (1.17 ± 0.05) mm^-1, 8 weeks: (0.81 ± 0.07) vs (1.17 ± 0.04) mm^-1, 12 weeks: (0.75 ± 0.03) vs (1.16 ± 0.05) mm^-1] as well as positive cell expression rate of COL2A1 and ACAN protein were significantly decreased in the model group, while the bone trabecular separation, Mankin score, OARSI score and the expression levels of IL-1β [4 weeks: (53.87 ± 2.32) vs (29.71 ± 3.26) pg/mL, 8 weeks: (56.31 ± 5.85) vs (27.70 ± 2.69) pg/mL, (58.59 ± 3.36) vs (25.34 ± 3.23) pg/mL] and TNF-α [4 weeks: (142.52 ± 14.33) vs (71.52 ± 6.68) pg/mL, 8 weeks: (153.94 ± 7.36) vs (75.45 ± 2.78) pg/mL, (160.60 ± 10.93) vs (75.67 ± 3.20) pg/mL] were significantly increased (all P < 0.05). Compared with the model group, the mechanical pain threshold, the thermal pain threshold, the bone volume fraction, trabecular thickness, and trabecular number [4 weeks: (1.09 ± 0.04) vs (0.92 ± 0.02) mm^-1, 8 weeks: (1.02 ± 0.15) vs (0.81 ± 0.07) mm^-1, 12 weeks: (1.00 ± 0.05) vs (0.75 ± 0.03) mm^-1] and positive cell expression rate in the COL2A1 and ACAN protein was significantly increased in the treatment group, while the bone trabecular separation, Mankin score, OARSI score and the expression level of IL-1β [4 weeks: (37.15 ± 7.16) vs (53.87 ± 2.32) pg/mL, 8 weeks: (41.56 ± 7.24) vs (56.31 ± 5.85) pg/mL, 12 weeks: (42.39 ± 3.41) vs (58.59 ± 3.36) pg/mL] and TNF-α [4 weeks: (84.49 ± 7.12) vs (142.52 ± 14.33) pg/mL, 8 weeks: (88.22 ± 3.25) vs (153.94 ± 7.36) pg/mL, 12 weeks: (90.31 ± 5.29) vs (160.60 ± 10.93) pg/mL] were significantly decreased (all P < 0.05). Compared with the 4-week model group, the trabecular thickness and the expression level of TNF-α in the 12-week model group were significantly increased, while the number of trabeculae and the positive cell expression rate of ACAN protein were significantly decreased (all P < 0.05).

ADSCs can relieve the pain symptoms of KOA, reduce joint inflammation, and may repair cartilage damage by promoting chondrogenesis, which has a certain timeliness, providing experimental basis for certain timeliness characteristics of clinical stem cell therapy for KOA.

Mesenchymal stem cells (MSCs) have shown great promise in the treatment of diabetic foot ulcers due to their multipotent differentiation potential, self-renewal capacity, and biological characteristics such as pro-angiogenesis, immunomodulation, and anti-inflammation. Numerous clinical studies and systematic reviews have demonstrated that MSC transplantation is generally safe, with a low incidence of serious adverse events and mild, reversible major side effects. MSCs can exert therapeutic effects by improving local ischemia, promoting angiogenesis, and accelerating wound healing. Some randomized controlled trials and meta-analyses have shown that they are superior to conventional treatments in terms of ulcer healing rate, limb perfusion indicators, and quality of life improvement. MSCs from different tissue sources each have their own advantages in terms of proliferation capacity, immunomodulatory effects, and clinical efficacy. However, the clinical translation of MSCs still faces challenges such as variations in cell quality, lack of standardization in preparation procedures, limitations in large-scale production, and unclear long-term safety and efficacy. Larger sample sizes and more rigorously designed clinical studies are still needed to further clarify the efficacy evaluation system and optimal application strategies, and promote the standardized and sustainable clinical application of MSCs in diabetic foot ulcers.

Hair follicle stem cells (HFSCs), a kind of adult stem cells located in the bulge region of hair follicles, participate in cyclical hair follicle renewal and skin wound repair. Current evidence indicates that Wnt/β-catenin, bone morphogenetic protein (BMP), and sonic hedgehog (Shh) signaling pathways, together with neural, metabolic, mechanical, and injury-related microenvironments, regulate the transition between quiescence and activation in HFSCs. Three-dimensional culture, organoids, gene editing, high-content imaging, and single-cell analysis have also played a promoting role in its functional studies and translational evaluation. HFSCs show potential for hair regeneration, wound repair, and tissue engineering; however, maintenance of stemness, cellular heterogeneity, delivery and integration efficiency, and long-term safety require further investigation. This review summarizes the morphology and distribution, proliferation and differentiation, phenotypic markers, regulatory signals, and research techniques of HFSCs, as well as evidence for their use in hair regeneration, wound repair, tissue engineering, and neural regeneration, providing a reference for mechanistic studies and translational evaluation of HFSC-related strategies.

Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders originating from hematopoietic stem cells, which are characterized by high heterogeneity and potentially aggressive behavior. Treatment selection is primarily determined by the patient's risk category and therapeutic urgency. Currently, hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for MDS. This article systematically reviews the pathogenesis of MDS and its association with transplant prognosis, clinical treatment strategies, and research progress in HSCT for MDS. Specifically, it focuses on the controversy and advantages of hypomethylating agents combined with venetoclax (HMA+VEN) as pre-transplant bridging therapy, the innovation of post-transplant cyclophosphamide (PTCy) in graft-versus-host disease (GVHD) prophylaxis strategies, precision selection of novel conditioning regimens, and the latest strategies for post-transplant relapse prevention and minimal residual disease (MRD) monitoring and management. The aim is to provide a reference for individualized treatment of MDS patients.

Dysregulated adaptive remodeling of the hematopoietic system under high-altitude hypoxic conditions constitutes the core cause of high-altitude polycythemia (HAPC), and the classic hypoxia-inducible factor-erythropoietin axis theory fails to fully elucidate the mechanisms underlying its pathological transition. Recent studies have revealed that hypoxia drives the expansion of a multipotent progenitor subset with high expression of transcription factor FOS, shifts lineage differentiation toward erythroid cells and establishes hypoxic hematopoietic memory. At the same time, ferroptosis in splenic macrophages impairs erythrocyte clearance and upregulated CD47 enables red blood cells to evade phagocytosis, with all these processes collectively contributing to HAPC pathogenesis. Genetic and inflammatory factors exacerbate individual variability. Based on the above pathological mechanisms, mesenchymal stem cell therapy delivers therapeutic benefits by stabilizing the hematopoietic microenvironment, relieving inflammation and oxidative stress, repairing multi-organ injuries and improving systemic oxygen supply to target both pathogenic origins and secondary lesions, yet its clinical application is currently restricted by bottlenecks such as severe cellular heterogeneity and inadequate targeted homing capacity. Therefore, future work should combine susceptibility gene screening with optimized stem cell technologies to advance the prevention and treatment of HAPC from symptomatic intervention toward precise regulation at the source of lesions.

A key objective in regenerative medicine is the development of "off-the-shelf" cell therapies that combine reparative potential with a strong safety profile. Multilineage-differentiating stress-enduring (Muse) cells are an endogenous subpopulation of mesenchymal stem cells, primarily characterized by stage-specific embryonic antigen-3 (SSEA-3) positivity, non-tumorigenicity, and the potential for tri-lineage differentiation. Their reparative mechanisms involve homing to damaged tissues mediated by the sphingosine-1-phosphate and its receptor 2 (S1P-S1PR2) axis, rapid in situ differentiation via the phagocytosis of apoptotic cell fragments, and immune tolerance conferred by the expression of human leukocyte antigen-G. The safety profile of Muse cells is predicated on a unique molecular regulatory network that maintains pluripotency through the tumor suppressor let-7, rather than through oncogenes. Preclinical studies have corroborated their reparative efficacy in various injury models, including those of the neurological, cardiovascular, and hepatic systems, while early clinical trials have demonstrated their favorable safety profile across multiple diseases. Although the clinical translation of Muse cells continues to face challenges such as the rarity of cell sources, scalable manufacturing, and discrepancies between preclinical and clinical outcomes, "cell-free" therapies and strategies aimed at activating endogenous Muse cells serve as noteworthy directions for future development.

Geriatric diabetes is a prevalent chronic metabolic disorder in the elderly population, and type 2 diabetes mellitus accounts for the vast majority of cases. Its core pathogenesis lies in pancreatic islet β-cell damage and insulin resistance. At present, there is no radical cure for this disease in clinical practice. Patients rely on long-term hypoglycemic drugs to maintain blood glucose homeostasis, while such treatments show limited efficacy in preventing and managing diabetic complications. As "seed cells" with self-renewal and multi-lineage differentiation potential, stem cells have achieved definite therapeutic effects in the treatment of various refractory diseases. Recent studies have verified that stem cells can exert hypoglycemic effects via regulating glucose metabolism, improving the secretory function of islet cells, promoting the proliferation and differentiation of insulin-secreting cells, repairing damaged pancreatic islet β-cells, facilitating pancreatic angiogenesis and tissue reconstruction, modulating immune function, alleviating chronic inflammatory responses, and enhancing insulin sensitivity of peripheral tissues. This paper systematically reviews the current research status of stem cells in the treatment of geriatric diabetes, analyzes the deficiencies of existing studies, and further explores the application value of stem cells from the perspective of action mechanisms, providing a theoretical basis for basic research and clinical transformation in this field.