Targeting the DNA repair pathway for breast cancer therapy: Beyond the molecular subtypes.

DNA repair is a vital mechanism in cells that protects against DNA damage caused by internal and external factors. It involves a network of signaling pathways that monitor and transmit damage signals, activating various cellular activities to repair DNA damage and maintain genomic integrity. Dysfunctions in this repair pathway are strongly associated with the development and progression of cancer. However, they also present an opportunity for targeted therapy in breast cancer. Extensive research has focused on developing inhibitors that play a crucial role in the signaling pathway of DNA repair, particularly due to the remarkable success of PARP1 inhibitors (PARPis) in treating breast cancer patients with BRCA1/2 mutations. In this review, we summarize the current research progress and clinical implementation of BRCA and BRCAness in targeted treatments for the DNA repair pathway. Additionally, we present advancements in diverse inhibitors of DNA repair, both as individual and combined approaches, for treating breast cancer. We also discuss the clinical application of DNA repair-targeted therapy for breast cancer, including the rationale, indications, and summarized clinical data for patients with different breast cancer subtypes. We assess their influence on cancer progression, survival rates, and major adverse reactions. Last, we anticipate forthcoming advancements in targeted therapy for cancer treatment and emphasize prospective areas of development.

Comparative life cycle assessment of the linear and circular wine industry chains: a case study in Inner Mongolia, China.

Environmental issues and the sustainability of the wine industry receive widespread public attention, but few studies address the environmental impact of the circular wine industry chain. Therefore, we applied the life cycle assessment (LCA) method to a wine enterprise in Inner Mongolia, China, to conduct a cradle-to-gate assessment and comparative analysis on the linear and circular wine industry chain scenarios. The results show that the circular industry chain (S2) has better environmental benefits; the total value of each environmental impact category of S2 is reduced by more than 80% compared with that of the linear industry chain (S1). The global warming potential of S1 is decreased from 4.88 kg CO2eq to 0.919 kg CO2eq for S2. Viticulture is the primary source of environmental problems in all life cycle stages of both scenarios, and electricity and diesel consumption are the key factors affecting the results. Our study shows that the optimization of S2 significantly improves resource efficiency and energy utilization and alleviates the environmental burden through proper waste recycling. Finally, we proposed optimization suggestions based on S2. This study provides scientific guidance for promoting the wine industry to build a circular industry chain and optimize the industrial structure, thus promoting the sustainable development of the industry.

Comprehensive analysis reveals potential hub genes and therapeutic drugs in an acquired lymphedema model.

Background: Acquired lymphedema is a common and often severe complication of breast cancer surgery and radiology that seriously affects patients' quality of life. Nevertheless, the pathogenesis for acquired lymphedema is complex and remains unclear. The aim of this study is to find out possible genetic markers and potential drugs for acquired lymphedema. Methods: First, the GSE4333 datasets, which include expression data for six female humanized hairless immunocompetent SKH-1 mice (the condition of whom mimics acquired lymphedema), were reanalyzed. According to the criteria of a fold change (FC) ≥1.4 and an adjusted P value <0.05, we identified the differentially expressed genes (DEGs) between a normal group and the lymphedema group. Next, we analyzed the Gene Ontology (GO) terms and enriched signaling pathways associated with these DEGs with an online tool DAVID. We also constructed protein-protein interaction (PPI) networks and selected meaningful gene modules for additional gene-drug interaction research. Finally, the extant drugs targeting these module genes were identified for further study of their therapeutic effects against acquired lymphedema. Results: A total of 481 DEGs were identified that were closely associated with the immune system, inflammatory response, and extracellular matrix (ECM) structural constituent terms, among others. Moreover, we identified the top 10 significant genes in the PPI networks and identified one extant drug, fiboflapon, that targets the ALOX5AP gene. Conclusions: We ultimately identified 10 hub genes, molecular mechanisms, and one extant drug related to acquired lymphedema. The findings identified targets and a potential drug for further research on acquired lymphedema.