Safety Profile Of Administration Research Articles

β-elemene, a sesquiterpene constituent from Curcuma phaeocaulis inhibits the development of endometriosis by inducing ferroptosis via the MAPK and STAT3 signaling pathways.

The rhizome of Curcuma phaeocaulis Valeton, Curcuma wenyujin Y.H. Chen & C. Ling, or Curcuma kwangsiensis S. G. Lee et C. F. Liang, commonly known as Wen-E-Zhu and E'zhu, has been utilized in traditional Chinese medicine for the treatment of cancer and gynecological diseases since antiquity. This traditional medicinal herb is highly esteemed for its efficacy in promoting blood circulation, dissolving blood stasis, reducing swelling, and alleviating pain. β-Elemene (β-ELE), a sesquiterpene compound derived from Curcuma phaeocaulis, has demonstrated potential in inhibiting tumor cell proliferation and inducing ferroptosis, which have been extensively studied in various malignant neoplasms. Previous studies have confirmed that Sparganium stoloniferum-Curcuma phaeocaulis containing β-ELE may possess anti-endometriotic properties. However, the exact mechanism underlying β-ELE's anti-endometriosis activity remains largely unknown and requires further research and investigation. To identify the anti-endometriosis target of β-ELE and elucidate the underlying molecular mechanism of β-ELE in endometriosis, focusing on inducing ferroptosis. The target pathway of β-ELE in endometriosis treatment was predicted through network pharmacology and bioinformatics analysis. Surface plasmon resonance-high performance liquid chromatography-protein mass spectrometry (SPR-HPLC-MS) and molecular docking were used to further identify the potential targets of β-ELE in endometriosis. The immortalized endometriosis epithelial cell line 12Z was used for in vitro study. The effect of β-ELE on cell proliferation and migration was detected by CCK-8, EdU and wound healing assay, and ultrastructural changes were examined via transmission electron microscopy. The effect of β-ELE-induced ferroptosis was determined by western blot, immunohistochemistry staining and flow cytometry. SPR affinity analysis was performed to specific the direct interaction between β-ELE and FTH1, FTL, GPX4, STAT3 and MAPK14. To establish a mouse model of endometriosis and to assess the inhibitory effects of β-ELE and ELE injection on endometriosis in vivo as well as safety profile of administration, and investigate the effects and underlying mechanisms of β-ELE and Elemene injection on ferroptosis in ectopic lesions. SPR-HPLC-MS was employed to identify 76 potential targets of β-ELE for endometriosis treatment, closely linked to ferroptosis. Molecular docking revealed that glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase 14 (MAPK14) are key action targets of β-ELE in endometriosis. Further investigations revealed that β-ELE inhibited the proliferation and migration of endometriotic cells in vitro while inducing ferroptosis, as evidenced by increased levels of iron, reactive oxygen species (ROS), and lipid peroxidation. In a mouse model, β-ELE inhibited the growth of endometriotic lesions, induced ferroptosis, suppressed fibrosis, and exhibited anti-endometriotic effects. Mechanistically, β-ELE downregulates the expression levels of GPX4, FTH1, and FTL and inhibited the phosphorylation of STAT3 and MAPK14, which may elucidate its underlying molecular mechanisms. This study demonstrates that the inhibitory effect of β-ELE on endometriosis by inducing ferroptosis in vitro and in vivo. Our results revealed that β-ELE exerts anti-endometriosis effects by inducing ferroptosis via the MAPK and STAT3 signaling pathways.

Comparison of Allergic Reactions to Intravenous and Intramuscular Pegaspargase in Children with Acute Lymphoblastic Leukemia

Pegaspargase (PEG) is a standard component of therapy for pediatric acute lymphoblastic leukemia (ALL). Because PEG preparations are bacterially derived, they are highly immunogenic. PEG has traditionally been delivered intramuscularly (IM), but over the last several years, more PEG has been given intravenously (IV) in order to provide a less painful and more convenient means of delivery. However, there are limited data comparing allergic reactions between IV and IM PEG recipients, especially in a large cohort of patients. We reviewed the charts of pediatric ALL patients diagnosed from 2006 to 2011 who received PEG at our institution and compared the incidence, time to onset of symptoms, reaction grade, and hospitalization rate for patients who had allergic reactions to PEG. Of 318 evaluable patients, 159 received IV and 159 received IM PEG. Thirty-one (19.5%) IV patients had an allergic reaction, compared to 17 (10.7%) IM patients (P = .028). Time to onset of symptoms was ≤ 30 minutes for 26 of 27 evaluable IV patients (96.3%) versus only two of 11 evaluable IM patients (18.2%; P < .001). Four of 31 IV patients (12.9%) and six of 17 IM patients (35.5%) required hospitalization (P = .134). There is increased incidence of allergy in patients who received IV PEG compared to IM. Grade of reaction was similar between IV and IM, but allergic reactions to IV PEG had a more rapid onset. While the risk of allergy may be increased, IV delivery appears to have an acceptable safety profile for administration in ALL patients.