To evaluate the feasibility and validity of chondrogenic differentiation of marrow clot after microfracture of bone marrow stimulation combined with bone marrow mesenchymal stem cells (BMSCs)-derived extracellular matrix (ECM) scaffold in vitro.BMSCs were obtained and isolated from 20 New Zealand white rabbits (5-6 months old). The 3rd passage cells were cultured and induced to osteoblasts, chondrocytes, and adipocytes in vitro, respectively. ECM scaffold was manufactured using the 3rd passage cells via a freeze-dying method. Microstructure was observed by scanning electron microscope (SEM). A full-thickness cartilage defect (6 mm in diameter) was established and 5 microholes (1 mm in diameter and 3 mm in depth) were created with a syringe needle in the trochlear groove of the femur of rabbits to get the marrow clots. Another 20 rabbits which were not punctured were randomly divided into groups A (n=10) and B (n=10): culture of the marrow clot alone (group A) and culture of the marrow clot with transforming growth factor beta3 (TGF-beta3) (group B). Twenty rabbits which were punctured were randomly divided into groups C (n=10) and D (n=10): culture of the ECM scaffold and marrow clot composite (group C) and culture of the ECM scaffold and marrow clot composite with TGF-beta3 (group D). The cultured tissues were observed and evaluated by gross morphology, histology, immunohistochemistry, and biochemical composition at 1, 2, 4, and 8 weeks after culture.Cells were successfully induced into osteoblasts, chondrocytes, and adipocytes in vitro. Highly porous microstructure of the ECM scaffold was observed by SEM. The cultured tissue gradually reduced in size with time and disappeared at 8 weeks in group A. Soft and loose structure developed in group C during culturing. Chondroid tissue with smooth surface developed in groups B and D with time. The cultured tissue size of groups C and D were significantly larger than that of group B at 4 and 8 weeks (P < 0.05); group D was significantly larger than group C in size (P < 0.05). Few cells were seen, and no glycosaminoglycan (GAG) and collagen type II accumulated in groups A and C; many cartilage lacunas containing cells were observed and more GAG and collagen type II were synthesized in groups B and D. The contents of GAG and collagen increased gradually with time in groups B and D, especially in group D, and significant difference was found between groups B and D at 4 and 8 weeks (P < 0.05).The BMSCs-derived ECM scaffold combined with the marrow clot after microfracture of bone marrow stimulation is effective in TGF-beta3-induced chondrogenic differentiation in vitro.
Abstract Background Lung cancer (LC) is the leading cause of cancer death in humans. tRNA-derived small RNA (tsRNA) is a novel biomarker that plays a crucial role in the genesis and development of LC. In this study, we aimed to investigate the value of differentially expressed tsRNA in LC through meta-analysis. Methods PubMed and Web of Science were searched until March 31, 2023. Diagnostic odds ratios (DORs) and area under the curves (AUCs) were used to evaluate the potential of tsRNAs as diagnostic markers for LC. Furthermore, hazard ratios (HRs) and 95% confidence intervals (95%CIs) were used to analyze the association of tsRNAs with LC prognosis. Results A total of 10 studies were included for analysis. Our results indicated that the combined DOR of total tsRNAs in LC diagnosis was 5.45, and AUC was 0.76. Subgroup analysis showed that high expression of tsRNAs in serum had higher diagnostic efficacy (DOR = 15.94, AUC = 0.87). Moreover, high expression of tsRNAs was associated with a worse prognosis in LC patients (HR = 1.59, 95%CI: 1.33–1.90). Conclusion Our findings suggest that high expression of tsRNAs has potential value in the diagnosis and prognosis of LC patients. However, further high-quality studies are needed to validate our results.
The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies in dermatomyositis (DM) is associated with an increased risk of developing rapidly progressive interstitial lung disease (RP-ILD) and a poor prognosis.
Molecular glue degraders induce "undruggable" protein degradation by a proximity-induced effect. Inspired by the clinical success of immunomodulatory drugs, we aimed to design novel molecular glue degraders targeting GSPT1. Here, we report the design of a series of GSPT1 molecular glue degraders. LYG-409, a 2H-chromene derivative, was identified as a potent, selective, and orally bioavailable GSPT1 degrader with excellent antitumor activity in vivo (anti-Acute Myeloid Leukemia MV4–11 xenograft model: TGI = 94.34% at 30 mg/kg; prostate cancer 22Rv1 xenograft model: TGI = 104.49% at 60 mg/kg) and in vitro (KG-1 cells: IC50 = 9.50 ± 0.71 nM, DC50 = 7.87 nM) mediated by the degradation of GSPT1. In conclusion, LYG-409 exhibits potent GSPT1 degradation activity, demonstrating promising therapeutic efficacy and favorable safety profile. However, its potential drug resistance profile needs to be thoroughly evaluated in comparison with existing treatments. We hope LYG-409 can provide a valuable direction for the development of GSPT1 degraders.
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