Potential roles and molecular mechanisms of bioactive ingredients in Curcumae Rhizoma against breast cancer.

BACKGROUND: Breast cancer is the most prevalent cancer worldwide, with high morbidity and mortality. Despite great advances in the therapeutic strategies, the survival rate in the past decades of patients with breast cancer remains unsatisfactory. Growing evidence has demonstrated that Curcumae Rhizoma, called Ezhu in Chinese, showed various pharmacological properties, including anti-bacterial, anti-oxidant, anti-inflammatory and anti-tumor activities. It has been widely used in Chinese medicine to treat many types of human cancer. PURPOSE: To comprehensively summarize and analyze the effects of active substances in Curcumae Rhizoma on breast cancer malignant phenotypes and the underlying mechanisms, as well as discuss its medicinal value and future perspectives. METHOD: We used "Curcumae Rhizoma" or the name of crude extracts and bioactive components in Curcumae Rhizoma in combination with "breast cancer" as key words. Studies focusing on their anti-breast cancer activities and mechanisms of action were extracted from Pubmed, Web of Science and CNKI databases up to October 2022. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: Crude extracts and 7 main bioactive phytochemicals (curcumol, ß-elemene, furanodiene, furanodienone, germacrone, curdione and curcumin) isolated from Curcumae Rhizoma have shown many anti-breast cancer pharmacological properties, including inhibiting cell proliferation, migration, invasion and stemness, reversing chemoresistance, and inducing cell apoptosis, cycle arrest and ferroptosis. The mechanisms of action were involved in regulating MAPK, PI3K/AKT and NF-κB signaling pathways. In vivo and clinical studies demonstrated that these compounds exhibited high anti-tumor efficacy and safety against breast cancer. CONCLUSION: These findings provide strong evidence that Curcumae Rhizoma acts as a rich source of phytochemicals and has robust anti-breast cancer properties.

S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome.

In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid ß-oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.