Dust storms and sandy dust events originating in arid and semi-arid areas can transport particulate material, pollutants, and potential transport long distances from their sources. Exposure to desert dust particles is generally acknowledged to endanger human health. However, most studies have examined anthropogenic particulate sources, with few studies considering contributions from natural desert dust. A systematic literature review was undertaken using the ISI Web of Knowledge and PubMed databases with the objective of identifying all studies presenting results on the potential health impact from desert dust particles across the world. This review reveals an imbalance between the areas most exposed to dust and the areas most studied in terms of health effects. Among the human health effects of dust storms are mortality and morbidity, arising from respiratory system, circulatory system, and other diseases. We summarize the quantitative results of current scientific health research and possible pathological mechanisms, and describe some of the many challenges related to understanding health effects from exposures to desert dust particles. Overall, for respiratory and circulatory mortality, both positive and negative associations have been reported for PM₁₀ of desert dust, but only a positive relationship was reported between PM_2.5–10 and mortality, and a positive relationship was also reported between PM_2.5 and human mortality. Future pathological studies should continue to focus on those mechanisms causing the most harmful effect of desert dust on respiratory and cardiovascular diseases. More attention should also be paid to the association between desert dust and the morbidity of other diseases, such as those affecting the reproductive system and nervous system.

Purpose: To investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) and the underlying molecular mechanism. Experimental Design: Using both FLT3-ITD cell lines and primary patient samples, Annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11–derived xenograft mouse model was used to assess in vivo efficacy of the combination of gilteritinib and venetoclax. Lentiviral overexpression of Mcl-1 was used to confirm its role in cell death induced by midostaurin or gilteritinib with venetoclax. Changes of Mcl-1 transcript levels were assessed by RT-PCR. Results: The combination of midostaurin or gilteritinib with venetoclax potently and synergistically induces apoptosis in FLT3-ITD AML cell lines and primary patient samples. The FLT3 inhibitors induced downregulation of Mcl-1, enhancing venetoclax activity. Phosphorylated-ERK expression is induced by venetoclax but abolished by the combination of venetoclax with midostaurin or gilteritinib. Simultaneous downregulation of Mcl-1 by midostaurin or gilteritinib and inhibition of Bcl-2 by venetoclax results in “free” Bim, leading to synergistic induction of apoptosis. In vivo results show that gilteritinib in combination with venetoclax has therapeutic potential. Conclusions: Inhibition of Bcl-2 via venetoclax synergistically enhances the efficacy of midostaurin and gilteritinib in FLT3-mutated AML. See related commentary by Perl, p. 6567

Atrazine, a widely used pesticide, is frequently detected in soil and surface water, which alarms epidemiologists and medical professionals because of its potential deleterious effects on health. Indeed, atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. Both animal and human studies have suggested that atrazine is possibly carcinogenic, although discrepant results have been reported. In this study, RM1 cells were used to explore the atrazine effects on prostate cancer. Proliferation, migration and invasion of RM1 cells were assessed by colony formation, wound-healing and invasion assays, respectively, after in vitro exposure to atrazine. In addition, an RM1 cell xenograft model was generated to evaluate the effects of atrazine in vivo. To explore the molecular mechanisms, qRT‑PCR, immunohistochemistry, and western blot analyses were employed to detect mRNA and protein levels of STAT3 signaling and cell cycle related proteins, including p53, p21, cyclin B1 and cyclin D1. Interestingly, RM1 cell proliferation was increased after treatment with atrazine, concomitantly with STAT3 signaling activation. These results suggest that atrazine promotes RM1 cell growth in vitro and in vivo by activating STAT3 signaling.

To date, there is no effective therapy available for the treatment of castration‑resistant prostate cancer (CRPC), and patients generally succumb to the disease within 2 to 4 years. In the progression of CRPC, androgen receptor (AR) and its splice variants play critical roles. Hence, it is necessary to develop a drug to inhibit the expression and activity of the full‑length and splice variants of AR for the treatment of CRPC. Erastin, as the first discovered drug to induce ferroptosis, has been studied in various types of cancer. However, there are few studies focusing on the relationship between erastin and AR. In the present study, western blotting, and sulforhodamine B cell viability, glutathione, lipid peroxidation and reactive oxygen species assays were performed to verify the ferroptosis of CRPC cells; reverse transcription‑quantitative polymerase chain reaction, dual‑luciferase reporter, and lentiviral packaging and lentivirus‑infected cell assays were employed to evaluate how erastin affects AR. A mouse xenograft assay was used to determine the underlying mechanism in vivo. Erastin, as a classical inducer of ferroptosis, can suppress the transcriptional activities of both the full‑length and splice variants in AR models in vitro and in vivo. In addition, when erastin was used for CRPC treatment combined with docetaxel, the growth inhibitory efficacy of docetaxel was found to be enhanced. Thus, these findings indicated that ferroptosis inducer erastin has potential in the treatment of CRPC via targeting AR.

Aldo-keto reductase family 1 member C3 (AKR1C3) is a key steroidogenic enzyme that is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). The aim of this study was to investigate the correlation between the expression level of AKR1C3 and the progression of PCa.