Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04964-z
Background Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5- induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1 by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024049
Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023286
Thioredoxin-interacting protein (TXNIP) is a crucial thioredoxin-binding protein that is recognized as a tumor suppressor in diverse malignancies, such as breast cancer, lung cancer, hepatocellular carcinoma, and thyroid cancer. However, the specific role and molecular mechanisms of TXNIP in the pathogenesis and progression of pancreatic cancer cells have not been determined. In this study, we investigate the relationship between TXNIP expression and overall survival prognosis in pancreatic cancer patients. Mechanistic studies are conducted to reveal the role of TXNIP in pancreatic cancer cell proliferation, migration, and regulation during malignancy. Our findings indicate that patients with high TXNIP expression have a more favorable prognosis. In vitro experiments with pancreatic cell lines show that overexpression of TXNIP suppresses the proliferation and migration of pancreatic cancer cells. Furthermore, we find that TXNIP inhibits the activation of the MAPK signaling pathway, thereby decreasing the malignant potential of pancreatic cancer. In conclusion, our study reveals TXNIP as a promising new predictive marker and therapeutic target for pancreatic cancer.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04964-z
Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population. Mesenchymal stem cells (MSCs) have emerged as a potential therapy, but the underlying mechanisms remain unclear. This study investigated the therapeutic effects of adipose-derived MSCs on imiquimod (IMQ)-induced psoriasis in mice and M5-induced psoriatic HaCaT keratinocytes in vitro. MSCs significantly ameliorated skin lesions, reduced inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and chemokines (MCP-1, CCL7, CCL20, CCL27), and restored skin barrier function by upregulating claudin-1. MSCs also normalized keratinocyte differentiation markers (increased KRT1, decreased KRT6). Amino acid metabolomics revealed that MSCs enhanced serine metabolism in mouse skin, upregulating phosphoserine phosphatase (PSPH). Knockdown of PSPH reversed the therapeutic effects of MSCs in vitro. Mechanistically, MSCs activated the PINK1-Parkin mitophagy pathway, as evidenced by increased PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I ratios, and decreased P62. This activation attenuated NLRP3 inflammasome activation and restrained keratinocyte hyperproliferation. The study concludes that MSCs alleviate psoriasis via PSPH-mediated activation of PINK1-Parkin mitophagy, suppressing NLRP3 inflammasome. Limitations include the need to identify specific MSC-secreted factors and lack of clinical validation. These findings provide a rationale for developing PSPH-targeted therapies for psoriasis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04964-z
Background: Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods: We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results: Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5-induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of these inflammatory factors by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions: The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21323
BACKGROUND: Currently, traditional Chinese medicine has been proven to play a significant role in combating rheumatoid arthritis. The efficacy and mechanisms of active components of Tripterygium wilfordii against rheumatoid arthritis have gained increasing recognition among researchers. OBJECTIVE: To summarize the research progress on the anti-rheumatoid arthritis effects of active components from Tripterygium wilfordii in vitro and in vivo. METHODS: Relevant literature published from inception to March 2025 was retrieved from CNKI, WanFang, VIP, and PubMed databases. Search terms included “rheumatoid arthritis, synovial cells, bone erosion, osteoclast, Tripterygium wilfordii, signal path” in Chinese and English. Eighty-seven articles were ultimately selected for review. RESULTS AND CONCLUSION: (1) Triptolide effectively alleviates joint inflammation and inhibits the abnormal proliferation and migration of fibroblast-like synoviocytes. Triptolide inhibits the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway mediated by interleukin-6 and soluble interleukin-6 receptor, thereby suppressing downstream pro-inflammatory cytokines (e.g., interleukin-6, interleukin-17), and time-dependently inhibits the expression of circRNA0003353 in rheumatoid arthritis fibroblast-like synoviocytes, while increasing the level of anti-inflammatory cytokine interleukin-4, reducing cell viability and migration, demonstrating dual potential for anti-inflammatory and inhibition of pathological synovial hyperplasia. (2) Celastrol significantly reduces joint swelling, synovial hyperplasia, inflammatory cell infiltration, and bone erosion. Celastrol inhibits the reactive oxygen species/nuclear factor kappa B/NOD-like receptor pyrin domain-containing protein 3 signaling pathway, reducing secretion of pro-inflammatory cytokines interleukin-1β and interleukin-18 in serum and immune cells. In collagen-induced arthritis rat models, celastrol induces autophagy and inhibits the phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway, significantly reducing levels of inflammatory cytokines such as tumor necrosis factor α and interleukin-1β, exerting cytoprotective and anti-inflammatory effects. (3) Wilforine can inhibit the inflammatory response of rheumatoid arthritis and potentially affect bone metabolism. In collagen-induced arthritis rat models, wilforine significantly downregulates levels of interleukin-6, interleukin-1β, and tumor necrosis factor α, and exerts therapeutic effects by inhibiting the abnormally activated Wnt/β-catenin signaling pathway. (4) The active components of Tripterygium wilfordii show good therapeutic effects in rheumatoid arthritis, but the mechanisms are complex, involving interactions of multiple genes, proteins, and signaling pathways. Current research has not fully elucidated the specific mechanisms, limiting their widespread clinical application. Future research should further explore the molecular mechanisms of active components and conduct large-scale clinical trials to verify efficacy and safety, while exploring combination strategies with other drugs to achieve better therapeutic outcomes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21502
OBJECTIVE: The therapeutic modalities of physical factor interventions for knee osteoarthritis have been increasingly diversified; however, comprehensive comparative evaluations of their efficacy remain limited. This study aims to compare the efficacy and safety of various physical factor therapies for knee osteoarthritis through a network meta-analysis. METHODS: Randomized controlled trials on physical factor therapy for knee osteoarthritis were retrieved from PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and CBM databases from inception to July 25, 2025. After literature screening and data extraction, the quality of included studies was assessed using the Cochrane risk-of-bias tool. Statistical analyses were performed using Stata 16.0 and RevMan 5.4.1. RESULTS: A total of 65 studies involving 3,418 patients (1,726 in treatment groups, 1,692 in control groups) were included, covering seven physical factor therapies. Network meta-analysis showed that for improving total effective rate, the top three interventions by surface under the cumulative ranking curve (SUCRA) were pulsed electromagnetic field + conventional rehabilitation, ultrasound + conventional rehabilitation, and transcutaneous electrical stimulation + conventional rehabilitation. For improving visual analogue scale (VAS) score, the top three were transcutaneous electrical stimulation + conventional rehabilitation, extracorporeal shock wave + conventional rehabilitation, and ultrasound + conventional rehabilitation. For improving WOMAC total score, the top three were ultrasound + conventional rehabilitation, pulsed electromagnetic field + conventional rehabilitation, and ultrasound + transcutaneous electrical stimulation + conventional rehabilitation. For reducing WOMAC stiffness score, the top three were transcutaneous electrical stimulation + conventional rehabilitation, ultrasound + conventional rehabilitation, and ultrasound + transcutaneous electrical stimulation + conventional rehabilitation. For improving SF-36 quality of life score, the top three were pulsed electromagnetic field + conventional rehabilitation, extracorporeal shock wave + conventional rehabilitation, and ultrasound + conventional rehabilitation. For improving Lysholm knee score, the top three were ultrasound + conventional rehabilitation, ultrasound + transcutaneous electrical stimulation + conventional rehabilitation, and extracorporeal shock wave + conventional rehabilitation. Regarding adverse events, no serious adverse events were reported; most studies reported only mild skin irritation or allergic reactions. CONCLUSION: Transcutaneous electrical stimulation combined with conventional rehabilitation showed superior advantages in improving VAS and WOMAC stiffness scores; ultrasound combined with conventional rehabilitation performed relatively better in improving Lysholm knee score and WOMAC total score; pulsed electromagnetic field combined with conventional rehabilitation had potential advantages in improving overall quality of life. Each physical factor has its unique advantages, but limited by the quality and quantity of included studies, these conclusions need to be verified by more high-quality, multi-center, large-sample randomized controlled trials.