Background: Mizaj (Temperament) is one of the fundamental concepts of Persian Medicine (PM) and identifying this concept is crucial for providing various healthcare recommendations and for the treatment of patients. In PM, various indices can indicate a person's Mizaj, one of them is the happiness of people. From this perspective, people with warm Mizaj are happier than people with cold Mizaj.

Background: Galbanic acid (GBA) is a sesquiterpene coumarin with valuable pharmacological effects. Adult T-cell lymphoma (ATL) is an aggressive lymphoid malignancy with low survival rate. Although arsenic trioxide (ATO) is a standard therapeutic agent for ATL treatment, efficacy of chemotherapy is limited due to chemoresistance of cells. Objective: The present study was carried out to investigate whether GBA in combination with ATO would improve cytotoxicity against ATL cells. Methods: GBA was isolated from the roots of Ferula szowitsiana by column chromatography on silica gel. MT-2 cells were treated with 20 µM GBA + 4 µM ATO and viability was evaluated by alamarBlue assay. Cell cycle was analyzed by PI staining, while the activity of P-glycoprotein (P-gp) was evaluated by mitoxantrone efflux assay. To understand the molecular mechanisms of GBA effects, the expression of NF-κB (RelA), P53, CDK4, c-MYC, c-FLIPL and c-FLIPS was evaluated by real-time PCR. Results: Combinatorial use of GBA + ATO significantly reduced the viability of MT-2 cells, and induced cell cycle arrest in the sub-G1 phase. GBA improved mitoxantrone accumulation in cells, indicating that this agent has inhibitory effects on the functionality of P-gp efflux pump. Moreover, real-time PCR analysis revealed that GBA + ATO negatively regulated the expression of P53, CDK4, c-FLIPL and c-FLIPS. Conclusion: Due to the interesting effects of GBA on the accumulation and toxicity of ATO, combinatorial use of these agents could be considered as a new therapeutic approach for ATL treatment.

Acute myeloid leukemia (AML) is a malignant disorder characterized by myeloid differentiation arrest and uncontrolled clonal expansion of abnormal myeloid progenitor cells. AML is the most common malignant bone marrow (BM) disease in adults and accounts for approximately 80% of adult leukemia cases. There has been little improvement in the treatment of patients with AML over the past decade. Cytogenetic and morphologic heterogeneity of AML and the difficulty in distinguishing leukemic stem cells (LSCs) from normal hematopoietic stem cells (HSCs) continue to be the major challenges in treating this malignancy. In recent years, intensive efforts have been made to explore novel potential markers for the efficient identification and characterization of leukemic stem cells. Aldehyde dehydrogenase (ALDH) is a potential target molecule that plays crucial roles in leukemic stem cell survival and multidrug resistance, mainly through its involvement in the detoxification of many endogenous and exogenous aldehydes. The selection and isolation of cancer stem cells based on high ALDH activity seem to be a useful approach in many human malignancies, especially leukemia. Moreover, it is worth mentioning that several previous studies have indicated that a high ALDH activity (classified as ALDHbr cells in flow cytometry) can act as an independent prognostic factor in several types of cancer. In the present review, we update and critically discuss the available data regarding the importance of ALDH activity in normal and leukemic stem cells and its potential diagnostic and therapeutic implications.

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