Narrow Results

We have previously shown that pachymic acid (PA) inhibited tumorigenesis of gastric cancer (GC) cells. However, the exact mechanism underlying the radiation response of GC was still elusive. To evaluate the effects of PA treatment on radiation response of GC cell lines both in vitro and in vivo, a colony formation assay and xenograft mouse model were employed. Changes in Bax and HIF1$\alpha$ expressions were assessed in GC cells following PA treatment. Luciferase reporter and chromatin immune-precipitation assays were carried out to investigate the regulation of Bax through HIF1$\alpha$. Stable HIF1$\alpha$ knockdown was introduced into GC cells to further study the mechanism underlying PA-enhanced response to radiation both in vitro and in vivo. PA greatly enhanced the sensitivity of GC cells to radiation in vitro and in vivo, upregulated Bax expression and inhibited hypoxia. Bax expression was under hypoxia inhibition, and PA increased Bax expression through repressing HIF1$\alpha$. Stable HIF1$\alpha$ overexpression in GC cells abolished the sensitizing effect of PA on GC cells to radiation both in vitro and in vivo. PA functions as a radiation sensitizing compound in GC. PA treatment induces the expression of pro-apoptotic factor Bax by inhibiting hypoxia/HIF1$\alpha$, supporting the therapeutic potential of PA in radiation therapy against GC.

Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos, has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1$\beta$, IL-6, and tumor necrosis factor $\alpha$ (TNF-$\alpha$) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86${}^{+}$) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206${}^{+}$) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF-$\kappa$B pathway activation via inhibiting NF-$\kappa$B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF-$\kappa$B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.