Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.

BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.

Investigating PM2.5 toxicity in highly polluted urban and industrial areas in the Middle East: human health risk assessment and spatial distribution.

Exposure to particulate matter (PM) can be considered as a factor affecting human health. The aim of this study was to investigate the concentration of PM2.5 and heavy metals and their influence on survival of A549 human lung cells in exposure to PM2.5 breathing air of Ahvaz city. In order to assess the levels of PM2.5 and heavy metals, air samples were collected from 14 sampling stations positioned across Ahvaz city during both winter and summer seasons. The concentration of heavy metals was determined using ICP OES. Next, the MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was employed to ascertain the survival rate of A549 cells. The findings from this research demonstrated that average PM2.5 of the study period was (149.5 µg/m3). Also, the average concentration of PM2.5 in the urban area in winter and summer was (153.3- and 106.9 µg/m3) and in the industrial area this parameter was (191.6 and 158.3 µg/m3). The average concentration of metals (ng/m3) of urban areas against industrial, Al (493 vs. 485), Fe (536 vs. 612), Cu (198 vs. 212), Ni (128 vs. 129), Cr (48.5 vs. 54), Cd (118 vs. 124), Mn (120 vs. 119), As (51 vs. 67), Hg (37 vs. 50), Zn (302 vs. 332) and Pb (266 vs. 351) were obtained. The results of the MTT assay showed that the highest percentage of cell survival according to the exposure concentration was 25 > 50 > 100 > 200. Also, the lowest percentage of survival (58.8%) was observed in the winter season and in industrial areas with a concentration of 200 µg/ml. The carcinogenic risk assessment of heavy metals indicated that except for Cr, whose carcinogenicity was 1.32E-03, other metals were in the safe range (10-4-10-6) for human health. The high concentration of PM2.5 and heavy metals can increase respiratory and cardiovascular diseases and reduce the public health level of Ahvaz citizens.