Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. PURPOSE: This study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. METHODS: In vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. RESULTS: Andro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. CONCLUSION: This study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway / 生物医学与环境科学（英文）

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

Discussion on Tuina Treatment for Acute Neck Type Cervical Spondylosis / 中国中医药信息杂志

Neck type cervical spondylosis, as one of the common types of cervical spondylosis, is a frequently occurring disease in orthopedics. The underlying pathogenetic basis is deficiency of positive qi (zhengqi). The disease is usually triggered by external contraction of cold in the neck area. The main clinical symptoms include pain in the occipital region, stiff neck and limitation of neck motion. Tuina (massage) is an effective treatment for this disease. It is effective in relieving symptoms as well as eliminating the underlying cause of the disease through warming yang and strengthening body resistance, regulating qi, and diagnosing and treating according to muscle and tendons conditions, and then address both the symptoms and root causes.

Reliability and validity of the Occupational Stress Scale for Chinese offshore oil platform workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the validity and reliability of the Occupational Stress Scale (OSS) for Chinese offshore oil platform workers.</p><p><b>METHODS</b>A 51-item self-administered questionnaire developed in the light of Cooper's questionnaire and company's special situation was used to investigate 561 subjects.</p><p><b>RESULTS</b>51 occupational stress items relating to offshore oil production were subjected to factor analysis, and nine latent factors were identified, which explained 62.5% of the total variance. According to the contents described by the items included in each factor, they were respectively defined as: "the interface between job and family/social life (factor 1)", "career and achievement (factor 2)", "safety (factor 3)", "management problem and relationship with others at work (factor 4)", "physical factors of workplace (factor 5)", "platform living environment (factor 6)", "role in management (factor 7)", "ergonomics (factor 8)" and "organization structure (factor 9)". Significant difference in the score of five factors was observed among 12 different job categories by analysis of variance. After adjusting for potential confounding factors (age, educational level), hierarchical multiple regression analysis indicated that the score of the OSS was significantly and positively correlated with the poor mental health of the workers (P < 0.01). The consistent test between OSS and each factor showed that Cronbach's alpha were 0.72 - 0.91.</p><p><b>CONCLUSION</b>The OSS is a valid and reliable tool for measuring occupational stress, and can be used to explore occupational stress and its influence on health and safety problems in offshore oil workers.</p>