Potential urinary biomarkers in young adults with short-term exposure to particulate matter and bioaerosols identified using an unbiased metabolomic approach.

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC-MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases.

[Therapeutic effect of lithium chloride combined with cyclosporine A on mouse model with aplastic anemia].

Wnt signaling has been shown to inhibit adipogenic differentiation while inducing the osteogenic pathway of bone marrow stromal cells (BMSC). Patients with aplastic anemia (AA) often show excess fat accumulation in the bone marrow, possibly due to overactivation of the adipogenic pathway. Therefore, an activator of the Wnt signaling may alleviate the symptoms by enhancing the inhibition on the differentiation of BMSC towards adipocytes. To judge this hypothesis, the therapeutic effects of Wnt signaling activator lithium chloride (LiCl) combined with the currently used immunosuppressor cyclosporine A (CsA) on mice with AA in vivo was investigated. Mouse model with AA was established and the disease was confirmed by increased fat cell counts and decreased hematopoietic cell counts in the bone marrow of these animals. These mice treated with CsA 50 mg/(kg·d) alone or together with LiCl 20 mg/(kg·d), once daily for 5 d, then at day 14, 21 and 28 after establishment of mouse model with AA, the treatment effects were observed, including peripheral blood cells, bone marrow mononuclear cells (BMMNC) count and bone marrow biopsy examination in each group. The results showed that compared with the AA group, Hb content, WBC and BMMNC counts of CsA group and the combination group significantly increased. HE staining of bone marrow biopsy sample showed that the fat cells were significantly reduced in the bone marrow cavity (P < 0.05). Compared with the CsA group, Hb content, WBC and BMMNC counts of the combination group significantly increased (P < 0.05); HE staining of bone marrow biopsy sample showed that fat cells were reduced, the hematopoiesis of bone marrow was close to the normal. It is concluded that Wnt signal activator (LiCl) combined with CsA displayed a better treatment effect on AA in mouse models than the effect of using CsA only. They can promote the hematopoietic function of bone marrow, which may correlate with inhibiting differentiation of bone marrow mesenchymal stem cells into the fat cells by Wnt signaling.