1.Nicotinic acid protects against hepatic ischemia-reperfusion injury via suppressing mitochondrial damage-induced ferroptosis
Qian Zeng ; Yina Sun ; Mengzhen Lei ; Zihan Liu ; Xijing Yan ; Rong Li ; Jun Zheng ; Jiandong Zha ; Lijun Zhang ; Xiaoling Guan ; Jia Yao
Liver Research 2025;9(4):324-337
Abstract
Background and aims
Hepatic ischemia-reperfusion injury (HIRI) is a major contributor to liver dysfunction and failure, particularly in the context of liver transplantation. Its pathogenesis is primarily driven by ferroptosis, oxidative stress, and mitochondrial dysfunction. Given the interplay among these mechanisms through redox imbalance and disrupted energy metabolism, nicotinic acid (NA)—recognized for its antioxidative and metabolic regulatory properties—emerges as a promising therapeutic candidate. This study aims to investigate the protective effects of NA on HIRI and elucidate its underlying mechanisms.
Methods
An HIRI model in mice and a hypoxia/reoxygenation (H/R) model in primary hepatocytes were established to evaluate the effects of NA treatment on oxidative stress. NA was administered prior to model induction. N-acetylcysteine (NAC) was used as a comparator. Comprehensive assessments of ferroptosis, oxidative stress, mitophagy, and mitochondrial biogenesis markers were conducted using Western blotting, immunohistochemistry, immunofluorescence, and biochemical assays.
Results
NA pretreatment reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (LDH) levels, suppressed inflammation by decreasing neutrophil infiltration and macrophage activation, and mitigated oxidative stress by lowering reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It enhanced antioxidant defenses, inhibited ferroptosis, and improved mitochondrial health through increased mitophagy, mitochondrial biogenesis, and mitochondrial permeability transition pore (mPTP) stabilization, leading to enhanced ATP production and mitochondrial function in HIRI.
Conclusions
NA improves mitochondrial function by promoting mitophagy and mitochondrial biogenesis, which reduces ferroptosis and oxidative stress, thereby alleviating HIRI.
2.Clinical significance of patterns of intrathoracic lymph node metastasis in non-small cell lung cancer:an analysis of 314 patients
Haichen ZHANG ; Jingbin SHI ; Jiandong ZHA
Chinese Journal of Radiation Oncology 2014;23(4):294-296
Objective To investigate the patterns of intrathoracic lymph node metastasis in nonsmall cell lung cancer (NSCLC) and to provide a theoretical basis for the delineation of radiotherapy target volume.Methods A retrospective analysis was performed on the clinical data of 314 NSCLC patients after operation.Our focus was to investigate the distribution characteristics and metastatic extent of intrathoracic lymph nodes and their relationship with tumor size,pathological type,and primary site.Comparisons between groups were made by one-way analysis of variance.Results The frequencies of metastases to lymph nodes at stations 4,5,7,10,and 11 were all above 12%,while those at stations 1,2,3,6,8,and 9 were all below 12%.The lymph node metastasis rate was similar on the primary tumor site (P =0.102).The patients with T3 and T4 NSCLC had a significantly higher frequency of N2 lymph node metastasis than those with T1 and T2 NSCLC (17.0% vs.11.6%,P =0.002) ;the patients with adenocarcinoma had a significantly higher frequency of N2 lymph node metastasis than those with squamous cell carcinoma (34.5 % vs.23.2%,P =0.008).Conclusions For patients with T3 and T4 NSCLC of adenocarcinoma subtype,we should highlight the lymph nodes at stations 4,5,7,10,and 11 when delineating the radiotherapy target volume after operation.


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