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Anlotinib has strong antiangiogenic effects and leads to vessel normalization. However, the "window period" characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs. In this study, through RNA sequencing (RNA-seq) and label-free quantitative proteomics analysis, we discovered that anlotinib regulated the expression of components of the extracellular matrix (ECM), leading to a significant reduction in ECM stiffness. Our bioinformatic analysis revealed a potential positive relationship between the ECM pathway and gefitinib resistance, poor treatment outcomes for programmed death 1 (PD-1) targeting, and unfavourable prognosis following chemotherapy in lung cancer patients. We administered anlotinib in combination with these antitumour drugs and visualized their distribution using fluorescent labelling in various tumour types. Notably, our results demonstrated that anlotinib prolonged the retention time and distribution of antitumour drugs at the tumour site. Moreover, the combination therapy induced notable loosening of the tumour tissue structure. This reduction was associated with decreased interstitial fluid pressure and tumour solid pressure. Additionally, we observed that anlotinib effectively suppressed the Ras homologue family member A (RhoA)/Rho-associated protein kinase (ROCK) signalling pathway. These findings suggest that, in addition to its antiangiogenic and vessel normalization effects, anlotinib can increase the distribution and retention of antitumour drugs in tumours by modulating ECM expression and physical properties through the RhoA/ROCK signalling pathway. These valuable insights contribute to the development of combination therapies aimed at improving tumour targeting in cancer treatment.

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PURPOSE: Nonalcoholic steatohepatitis (NASH) has been an increasingly significant contributor to hepatocellular carcinoma (HCC). Understanding the progression from NASH to HCC is critical to early diagnosis and elucidating the underlying mechanisms. RESULTS: 5 significant prognostic genes related to NASH-HCC transformation were identified through algorithm selection, which were ME1, TP53I3, SOCS2, GADD45G and CYP7A1. A diagnostic model for NASH prediction was established (AUC=0.988). TP53I3 and SOCS2 were selected as potential critical genes in the progression of NASH-HCC by external dataset validation and in vitro experiments on NASH and HCC cell lines. Immune infiltration analysis illustrated the correlation between 5 significant prognostic genes and immune cells. Single-cell analysis identified hepatocytes related to NASH-HCC transformation markers, revealing their promoting role in the transformation from NASH to HCC. CONCLUSION: With bulk-seq analysis and single-cell analysis, 5 significant prognostic genes related to NASH-HCC transformation were identified and validated at both dataset and in vitro experiment level. Among them, TP53I3 and SOCS2 might be potential critical genes in NASH-HCC progression. Single-cell analysis identified and revealed the critical role that NASH-HCC related hepatocytes play in NASH-HCC tansformation. Our research may introduce a new perspective to the diagnosis, treatment of NASH-related HCC.

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Degradation of organics in high-salinity wastewater is beneficial to meeting the requirement of zero liquid discharge for coking wastewater treatment. Creating efficient and stable performance catalysts for high-salinity wastewater treatment is vital in catalytic ozonation process. Compared with ozonation alone, Mn and Ce co-doped γ-Al2O3 could remarkably enhance activities of catalytic ozonation for chemical oxygen demand (COD) removal (38.9%) of brine derived from a two-stage reverse osmosis treatment. Experimental and theoretical calculation results indicate that introducing Mn could increase the active points of catalyst surface, and introducing Ce could optimize d-band electronic structures and promote the electron transport capacity, enhancing HO• bound to the catalyst surface ([HO•]ads) generation. [HO•]ads plays key roles for degrading the intermediates and transfer them into low molecular weight organics, and further decrease COD, molecular weights and number of organics in reverse osmosis concentrate. Under the same reaction conditions, the presence of Mn/γ-Al2O3 catalyst can reduce ΔO3/ΔCOD by at least 37.6% compared to ozonation alone. Furthermore, Mn-Ce/γ-Al2O3 catalytic ozonation can reduce the ΔO3/ΔCOD from 2.6 of Mn/γ-Al2O3 catalytic ozonation to 0.9 in the case of achieving similar COD removal. Catalytic ozonation has the potential to treat reverse osmosis concentrate derived from bio-treated coking wastewater reclamation.

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Breast cancer poses a significant risk to women worldwide, yet specific role of SERPINA gene family in breast cancer remains unclarified. Data were collected from online databases. SERPINA family gene expression was presented, and prognosis value was evaluated. Multi-omics methods were employed to explore the SERPINA-related biological processes, followed by comprehensive analyses of their roles in breast cancer. Single-cell data were analyzed to characterize the SERPINA family gene expression in different cell clusters. We selected SERPINA5 as the target gene. Via pan-cancer analysis, SERPINA5 was also investigated in various cancers. The experimental validation was conducted in MDA-MB-231 cell line eventually. SERPINA family showed differential expression in breast cancer, which were mainly expressed in myeloid cells, epithelial cells, and dendritic cells. SERPINA5 expression was upregulated in breast cancer, which was associated with a better prognosis. Immune infiltration illustrated the positive correlativity between SERPINA5 intensity and eosinophilic recruitment. Pan-cancer analysis indicated the function of SERPINA5 as a potential biomarker in other cancers. Finally, experimental validation demonstrated that SERPINA5 contributes to lower invasion and metastatic potential of breast cancer cells. With bioinformatics analysis, the significant role SERPINA family genes functioned in breast cancer was comprehensively explored, with SERPINA5 emerging as a key gene in suppressing breast cancer progression.

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Objective: The aim of the study is to explore the curative effect of Yangxin Dingji capsule combined with mexiletine hydrochloride on postoperative ventricular arrhythmia (VA) and its influences on vascular endothelial function in coronary bifurcation lesions (CBL). Methods: A total of 110 patients with CBL admitted to the hospital were enrolled as research subjects between January and December 2021. According to the random number table method, they were divided into a combination group and control group, with 55 cases in each group. The control group was treated with mexiletine hydrochloride, while the combination group was additionally treated with Yangxin Dingji capsules. All were continuously treated for 4 weeks. The clinical response rate between the two groups was compared. The frequencies of 24 h paroxysmal atrial fibrillation, premature atrial contraction, and premature ventricular contraction were compared by the Holter monitoring. The whole blood low-shear viscosity, whole blood high-shear viscosity, and fibrinogen (Fb) in both groups were measured by a full-automatic blood flow analyzer. The levels of plasma nitric oxide (NO), endothelin-1 (ET-1), and von Willebrand factor (vWF) were detected by the nitrate reductase method and enzyme-linked immunosorbent assay (ELISA). During treatment, the occurrence of adverse reactions (vomiting, loss of appetite, dry mouth, diarrhea, nausea) in both groups was statistically analyzed. Results: After treatment, the total response rate of treatment in the combination group was significantly higher than that in the control group (P < 0.05). After treatment, frequencies of paroxysmal atrial fibrillation, premature atrial contraction, and premature ventricular contraction in the combination group were significantly lower than those in the control group (P < 0.05). Whole blood low-shear viscosity, whole blood high-shear viscosity, and the Fb level were significantly lower than those in the control group (P < 0.05). After treatment, the NO level in the combination group was significantly higher than that in the control group (P < 0.05), while levels of ET-1 and vWF were significantly lower than those in the control group (P < 0.05). During treatment, there was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). Conclusion: Yangxin Dingji capsule combined with mexiletine hydrochloride can significantly improve clinical effects in CBL patients, improve VA and vascular endothelial function, and reduce plasma viscosity without increasing the incidence of adverse reactions.

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OBJECTIVE: To investigate the influence of preventive pericardial devascularization on the life quality of patients with advanced schistosomiasis. METHODS: The clinical data of advanced schistosomiasis patients who received the preventive pericardial devascularization from January 2000 to December 2009 (140 cases) were collected and analyzed retrospectively, and other 81 cases without preventive pericardial devascularization served as controls. Results Compared with that of the control group, the long term upper gastrointestinal rebleeding within 3 years of the study group was much fewer (P < 0.01), while that of more than 5 years was fewer (P < 0.05); there were no differences in ascites and hepatic coma between the two groups (P > 0.05); the abilities of daily life and labor of the study group were much better than those of the control group (P < 0.01), and those of taking care of themselves and lost ability of labor were not significant between the two groups (P > 0.05); the long term death rate after surgery of the study group was significantly lower than that of the control group (P < 0.05). Conclusion The effect of preventive pericardial devascularization in the treatment of advanced schistosomiasis is reliable and the life qualities of the patients improve.

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