Bax Recombinant Rabbit Monoclonal Antibody

Hepatic ischemia-reperfusion injury (IRI) poses a significant clinical challenge in liver surgery and transplantation, primarily mediated through oxidative stress, mitochondrial dysfunction, and inflammatory activation. Herein, we developed SOD2-Res@CVs, an engineered vesicular platform combining SOD2-overexpressing mesenchymal stem cell-derived vesicles with liver-targeted and ROS-responsive resveratrol (Res)-loaded liposomes for multi-mechanistic intervention. In vivo imaging demonstrated that SOD2-Res@CVs selectively accumulated in IRI-damaged hepatic tissues. Within oxidative stress microenvironments, the system exhibited responsive liberation of SOD2 and resveratrol, which cooperatively mitigated oxidative damage through redox homeostasis modulation - evidenced by reduced lipid peroxidation (MDA suppression) and enhanced antioxidant defense (GSH/SOD2 upregulation). This therapeutic cascade facilitated mitochondrial structural and functional restoration via multiple pathways: Resveratrol specifically activated PINK1-mediated mitophagy, as confirmed by increased LC3 and beclin-1 expression, thereby promoting selective clearance of depolarized mitochondria. Comparative analyses revealed SOD2-Res@CVs' superior therapeutic efficacy over individual components in histological recovery and organ function preservation. Transcriptomic profiling further validated the system's multi-target regulatory capacity, highlighting its concurrent suppression of oxidative stress pathways, mitigation of inflammatory signaling, and improvement of mitochondrial bioenergetics during IRI progression. This study establishes SOD2-Res@CVs as a multifunctional nanotherapeutic strategy that harmonizes spatial targeting with pathological microenvironment responsiveness and a promising approach for liver protection in transplantation.

The sympathetic adrenergic nerves (SAN) play a significant role in the malignant transformation of breast cancer cells through the activity of norepinephrine (NE). However, the role of tyrosine hydroxylase (TH), a key enzyme of the NE synthesis, in the interaction between the SAN and triple-negative breast cancer (TNBC) cells has not been sufficiently explored, and whether TH can be a therapeutic target for TNBC has not been reported. TH expression in TNBC was examined by analyzing data from an online database and immunohistochemical analysis of our clinical samples. Cell proliferation and drug sensitivity were assessed upon coculture with fluorescently labeled cells using IncuCyte. Changes in the expression of DNA damage and apoptosis-associated proteins were assessed by western blotting. TH expression and NE synthesis in PC12 cells after their coculture with TNBC cells were measured by RT–qPCR, immunofluorescence, and ELISA. RNA sequencing was conducted on the cells before and after coculture. TH expression was relatively high in TNBC tumor tissues and closely associated with prognosis. SAN promoted TNBC cell proliferation through NE and reduced TNBC cell sensitivity to chemotherapeutic agents. Additionally, tumor cells induced TH expression in PC12 cells through nerve growth factor (NGF) secretion. Knocking down TH and using TH inhibitors effectively reversed the proliferation-promoting and drug sensitivity-reducing effects of SAN in TNBC cells. TH may be a central molecule in the positive feedback loop between TNBC cells and SAN. TH is a potential prognostic biomarker and can also serve as a therapeutic target for TNBC. Key messages The overexpression of the sympathetic nerve biomarker tyrosine hydroxylase (TH) in triple-negative breast cancer (TNBC) is an indicator for clinical staging, prognosis, and targeted therapy. There is a feedback loop where TH in nerves produces NE, worsening TNBC and reducing chemotherapy effectiveness. TNBC cell then increases TH expression, further boosting NE production. Furthermore, blocking the activity of TH could effectively inhibit this phenotype. Graphical