Triton X-100 曲拉通X-100

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally, owing to its high recurrence rate of 50 to 70% within five years. Despite known associations of certain DNA damage and repair (DDR) genes with tumor recurrence and drug resistance, a comprehensive understanding of DDR pathways’ role in predicting HCC recurrence and therapeutic responses remains elusive. Addressing this gap could offer significant advancements in prognostic and therapeutic strategies for HCC. This study used 769 RNA sequencing samples from public datasets and 53 samples from Xiangya Hospital for DDR model training and validation. It came out that DDR pathways were significantly enriched in samples with P53 mutations. Next, among the 173 combinations of algorithms and parameters, CoxBoost + RSF, Lasso [fold = 10] + RSF, and Lasso [fold = 50] + RSF demonstrated the best performance. The average AUC values of 1 to 5 years and the average concordance index (C-index) value were around 0.7. The risk scores were increased in tumors with recurrence, P53 mutation, and higher TNM stages. High-risk groups, characterized by enriched DDR pathways, exhibited lower CD8 + T cell infiltration and poorer responses to immunotherapy using atezolizumab and bevacizumab, emphasizing the potential of DDR signatures as valuable prognostic and therapeutic biomarkers. In conclusion, the DDR signatures associated with P53 mutations can predict recurrence and therapeutic response in HCC, highlighting their potential as prognostic and therapeutic biomarkers.

Background: Hypoxic-ischemic brain damage (HIBD) is a prevalent brain injury with high mortality and morbidity. It results from hypoxia and ischemia of the brain due to various perinatal factors. A previous study showed that knockdown of programmed cell death factor 4 (PDCD4) could reduce infarction injury resulting from ischemia/reperfusion injury. However, exact mechanism by which PDCD4 acts in HIBD is not yet understood. Our aim in present investigation was to investigate the function and mechanism of PDCD4 in alleviating HIBD. Methods: An HIBD model was developed using neonatal rats. After 48 h of modeling, short-term neurological function was evaluated and the brain tissue removed for assessment of cerebral infarct volume and brain water content (BWC). A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) was also constructed. Overexpression or knockdown of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) or PDCD4 was performed in pretreated cells. Results: The geotaxis reflex time, cerebral infarct volume, and BWC all increased after HIBD in this neonatal rat model. Additionally, the levels of PDCD4 and of the N6-Methyladenosine (m6A) reader protein IGF2BP3 were increased in HIBD rats and OGD/R-stimulated pheochromocytoma (PC12) cells relative to controls. Moreover, OGD/R-stimulated pheochromocytoma PC12 cells showed decreased cell viability, increased apoptosis, and elevated Interleukin 6 (IL-6), Interleukin 1 β (IL-1β), and tumor necrosis factor-α (TNF-α) contents. These features were reversed after knocking down IGF2BP3. The interaction between IGF2BP3 protein and PDCD4 mRNA was confirmed by RNA immunoprecipitation and RNA pull-down assays. Furthermore, knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells reduced cell damage via down-regulation of PDCD4. Finally, the IGF2BP3/PDCD4 axis alleviated OGD/R-induced cell injury in primary cortical neurons (PCNs). Conclusions: PDCD4 and m6A reader protein IGF2BP3 were up-regulated in an HIBD neonatal rat model. Knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells or PCNs alleviated cell damage through reducing PDCD4.

Background: Vascular damage is a major consequence of bone fracture. Taohong Siwu decoction (TSD) can raise the expression of vascular endothelial growth factor (VEGF) in fracture healing. However, its molecular mechanism in promoting angiogenesis is still unknown. The aim of this study was to investigate the potential mechanisms of TSD in the regulation of osteo-angiogenesis in fracture healing. Methods: A rat tibial fracture model was established. After low- (4.5 g·kg -1 ), medium- (9 g·kg -1 ), and high-dose TSD (18 g·kg -1 ) and panax notoginsenoside (25 mg kg -1 ) treatment, hematoxylin-eosin staining was employed to visualize pathological changes in bone tissues. The levels of cytokines (interleukin (IL)-2, tumor necrosis factor- α (TNF- α ), IL-6, and IL-1 β ), thromboxane B2 (TXB2), and 6 ketone prostaglandin F1 α (6-Keto-PGF1 α ) were quantified by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to identify the rat aortic endothelial cells (RAECs). Control serum, 10% TSD-containing serum, and 10% TSD-containing serum combined with hypoxia-inducible factor-1 α (HIF-1 α ) inhibitor were used to treat the RAECs and rat osteoblasts. Transwell migration assay was utilized to examine the migration of the RAECs. The Matrigel tubulogenesis assay was used for the assessment of angiogenesis. The expression of angiogenesis- (von Hippel-Lindau tumor suppressor (VHL), HIF-1 α , VEGF, angiopoietin-2 (Ang-2), and pVHL) and osteogenesis-related (alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteopontin-1 (OPN-1)) protein and gene was detected by western blot and quantitative real-time PCR (qRT-PCR). Results: Compared with the model group, TSD increased the trabecular bone areas, numbers, and thicknesses in fractured rats. In the plasma, the levels of cytokines and TXB2 in the middle- and high-dose TSD group were significantly lower than those in the model group ( P < 0.01). The 6-keto-PGF1 α content was increased by middle- and high-dose TSD intervention ( P < 0.01). Compared to the control serum group, the angiogenesis and migration of the RAECs were enhanced in the TSD group ( P < 0.001). The expression of HIF-1 α , VEGF, and Ang-2 in the TSD group upregulated significantly ( P < 0.001). VHL and pVHL were inhibited under TSD-containing serum treatment ( P < 0.001). ALP, Runx2, and OPN-1 were increased obviously in the TSD group ( P < 0.001). Nevertheless, the HIF-1 α inhibitor reversed these changes ( P < 0.001). Conclusion: TSD promotes angiogenesis and osteogenesis by regulating the HIF-1 α signaling pathway. Meanwhile, it can effectively reduce the risk of inflammation and improve blood circulation.

Background: Hyperglycemia is widespread in the world’s population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. Methods: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1β, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. Results: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase-1, increase the levels of IL-1β, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1β, IL-18, ROS, MDA, and LDH. Conclusion: EPCs exosomal LINC01963 play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.