circ_SIRT1 upregulates ATG12 to facilitate Imatinib resistance in CML through interacting with EIF4A3.

Imatinib is the current gold standard for patients with chronic myeloid leukemia (CML). However, the primary and acquired drug resistance seriously limits the efficacy. To identify novel therapeutic target in Imatinib-resistant CML is of crucial clinical significance. CircRNAs have been demonstrated the essential regulatory roles in the progression and drug resistance of cancers. In this study, we identified a novel circRNA (circ_SIRT1), derived from the SIRT1, which is up-regulated in CML. The high expression of circ_SIRT1 is correlated with drug resistance in CML. Knockdown of circ_SIRT1 regulated K562/R cells viability, invasion and apoptosis. Besides, the inhibition of circ_SIRT1 attenuated autophagy level and reduced IC50 to Imatinib of K562/R cells. Mechanistically, circ_SIRT1 directly binds to the transcription factor Eukaryotic Translation Initiation Factor 4A3(EIF4A3) and regulated EIF4A3-mediated transcription of Autophagy Related 12 (ATG12), thereby affecting Imatinib resistance and autophagy level. Overexpression of ATG12 reversed the regulative effects induced by knockdown of circ_SIRT1. Taken together, our findings revealed circ_SIRT1 acted as a potential tumor regulator in CML and unveiled the underlying mechanism on regulating Imatinib resistance. circ_SIRT1 may serve as a novel therapeutic target and provide crucial clinical implications for Imatinib-resistant CML treatment.

The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies.

RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.

Nano titanium dioxide induces the generation of ROS and potential damage in HaCaT cells under UVA irradiation.

Nano titanium dioxide (nano-TiO2) is frequently used in cosmetics, especially in sunscreen. Nano-TiO2 has been reported to be an efficient photocatalyst, which is able to produce reactive oxygen species (ROS) under UVA irradiation. However, the effects and mechanisms of skin toxicity caused by nano-TiO2 remain unclear. In this study, we explored the cytotoxicity and oxidative stress induced by nano-TiO2 under UVA irradiation with different crystal forms (anatase, rutile and anatase/rutile) and sizes (4 nm, 10 nm, 21 nm, 25 nm, 60 nm) in human keratinocyte HaCaT cells. Intracellular distribution of nano-TiO2, cell viability, intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), super oxide dismutase (SOD) activity and Malondialdehyde (MDA) content were measured. The results showed that nano-TiO2 (10-200 microg/ml) significantly reduced cell viability in a dose-dependent manner in HaCaT cells. The cell viability was 76.9%, 60.2%, and 44.1% following nano-TiO2 (4 nm), nano-TiO2 (10 nm) and P25 treatment at the concentration of 200 microg/ml, respectively (P < 0.01). Nano-TiO2 induced ROS resulted in oxidative stress in these cells by reducing SOD and increasing MDA levels. The MMP of the cells was decreased significantly (P < 0.01) while the apoptosis rate was increased. Anatase and amorphous forms of nano-TiO2 showed higher cytotoxicity than the rutile form. The results indicated that nano-TiO2 could induce the generation of ROS and damage HaCaT cells under UVA irradiation.

Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure.

The present study investigated the penetration and potential toxicity of titanium dioxide (TiO(2)) nanoparticles following its dermal exposure in vitro and in vivo. In vitro, after exposure to isolated porcine skin for 24h, titanium dioxide nanoparticles of carious sizes cannot penetrate through stratum corneum. Interestingly, when studied in vivo, quite different results were obtained. After topically applied on pig ear for 30 days, TiO(2) nanomaterials (4 nm and 60 nm) can penetrate through horny layer, and be located in deep layer of epidermis. Furthermore, after 60 days dermal exposure in hairless mice, nano-TiO(2) particles can penetrate through the skin, reach different tissues and induce diverse pathological lesions in several major organs. Notably, P25 (21 nm) TiO(2) nanomaterials shows a wider tissue distribution, and can even be found in the brain without inducing any pathological changes. Among all of the organs examined, the skin and liver displayed the most severe pathological changes that correspond to the significant changes in SOD and MDA levels. These results suggest that the pathological lesions are likely to be mediated through the oxidative stress induced by the deposited nanoparticles. Accordingly, the collagen content expressed as HYP content are also significantly reduced in mouse skin samples, indicating that topically applied nano-TiO(2) in skin for a prolonged time can induce skin aging. Altogether, the present study indicates that nanosize TiO(2) may pose a health risk to human after dermal exposure over a relative long time period.

[Linguistic-cultural differences between Chinese and Western medicine and English translation of Chinese medicine].

This paper explores the influences of linguistic-cultural differences between Chinese and Western medicine on the English translation of Chinese medicinal terms/literature from such aspects as ideographic, phonetic writings and thinking modes, Chinese and Western medical terms, as well as Classic literature of Chinese medicine and medical English.

[Comments on "A practical dictionary of Chinese medicine" by Wiseman].

At least 24 Chinese-English dictionaries of Chinese Medicine have been published in China during the recent 24 years (1984-2003). This thesis comments on "A Practical Dictionary of Chinese Medicine" by Wiseman, agreeing on its establishing principles, sources and formation methods of the English system of Chinese medical terminology, and pointing out the defect. The author holds that study on the origin and development of TCM terms, standardization of Chinese medical terms in different layers, i.e. Chinese medical in classic, in commonly used modern TCM terms, and integrative medical texts, are prerequisites to the standardization of English translation of Chinese medical terms.

[The influence of Huang di nei jing (Huangdi's inner classic) on Shuo wen jie zi (the origin of Chinese characters)].

It is very likely that The Origin of Chinese Characters is influenced by Huang Di's Inner Classic after investigating the author of The Origin of Chinese Characters and identifying the publishing times of them. The following conclusions are reached through comparing and analyzing thinking modes, philosophical conception, and knowledge of human anatomy, disease and treatment in them: the knowledge of traditional Chinese medicine (TCM) contained in The Origin of Chinese Characters is in direct line of succession with the Inner Classic; the universe and ecomedical thinking modes of "heaven-earth-human being" in The Origin of Chinese Characters and the Inner Classic respectively are cut from the same cloth; the theories of qi, yin-yang, and the five phases, the theoretical foundation of the Inner Classic, can be traced back to their sources through The Origin of Chinese Characters; The Origin of Chinese Characters traces back to characters' origin and original meanings through analyzing their structures, therefore, the book is important for us to study and read the Inner Classic, and to probe into the origin of TCM as well.