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Mercury is a heavy metal toxicant that is prevalent throughout the environment. Organic forms of mercury, such as methylmercury (MeHg), can cross the placenta and can lead to lasting detrimental effects in the fetus. The toxicological effects of MeHg on the placenta itself have not been clearly defined. Therefore, the purpose of the current study was to assess the transport of MeHg into placental syncytiotrophoblasts and to characterize the mechanisms by which MeHg exerts its toxic effects. Cultured placental syncytiotrophoblasts (BeWo) were used for these studies. The transport of radioactive MeHg was measured to identify potential mechanisms involved in the uptake of this compound. The toxicological effects of MeHg on BeWo cells were determined by assessing visible pathological change, autophagy, mitochondrial viability, and oxidative stress. The findings of this study suggest that MeHg compounds are transported into BeWo cells primarily by sodium-independent amino acid carriers and organic anion transporters. The MeHg altered mitochondrial function and viability, decreased mitophagy and autophagy, and increased oxidative stress. Exposure to higher concentrations of MeHg inhibited the ability of cells to protect against MeHg-induced injury. The findings show that MeHg is directly toxic to syncytiotrophoblasts and may lead to disruptions in the fetal/maternal transfer of nutrients and wastes. [ABSTRACT FROM AUTHOR]

Background: Immunomodulatory effects of macrolides in chronic inflammation are well known. In this study, we tested our hypothesis that azithromycin (AZT) can decrease inflammation in pediatric patients with sickle cell disease (SCD)., Methods: The use of AZT as an anti-inflammatory agent was evaluated in double-blind, placebo-controlled, cross-over study for 8 weeks of treatment with 8 weeks of washout. Blood samples were collected before (PRE) and after (POST) each 8-week treatment period. Repeated measures analysis of variance (ANOVA) with post hoc multiple comparison procedures and Chi-square test were used for statistical analysis of the data. Complete blood count, distribution of the lymphocyte subsets, and plasma levels of markers of vascular damage were analyzed., Results: A significant decrease in the number of leucocytes and granulocytes was observed in AZT group following treatment. An opposite dynamic was observed in placebo group; numbers of granulocytes significantly increased at POST interval. All markers of vascular damage were reduced in AZT group at POST interval with overall significance (P = 0.026). The most prominent significant changes were observed in levels of myeloid-related protein 8/14 (MRP8/14), lipocalin A (NGAL), matrix metalloproteinases (MMP) 9, and insulin-like growth factor-binding protein (IGFBP) 4. Plasma level of C-reactive protein (CRP) was significantly decreased in AZT group as well., Conclusions: Data suggested that AZT may be beneficial in management of microvascular injury in SCD., Competing Interests: Authors declare no conflict of interest., (Copyright 2021, Uchakin et al.)

Elemental mercury (Hg 0 ) contamination in artisanal and small-scale gold mining (ASGM) communities is widespread, and Hg 0 -contaminated tailings are often reprocessed with cyanide ( - CN) to extract residual gold remaining after amalgamation. Hg 0 reacts with - CN under aerobic conditions to produce Hg(CN) 4 2- and other Hg(CN) n n -2 complexes. The production of solvated Hg(CN) n n -2 complexes increases upon agitation in the presence of synthetic and authentic Hg 0 -contaminated tailings that aid in dispersing the Hg 0 , increasing its reactive surface area. Adult rats were exposed to various concentrations of Hg(CN) 2 , and accumulation in organs and tissues was quantified using direct mercury analysis. The primary site of Hg(CN) 2 accumulation was the kidney, although accumulation was also detected in the liver, spleen, and blood. Little accumulation was observed in the brain, suggesting that Hg(CN) 2 complexes do not cross the blood-brain barrier. Renal tissue was particularly sensitive to the effects of Hg(CN) 2 , with pathological changes observed at low concentrations. Hg(CN) 2 complexes are handled by mammalian systems in a manner similar to other inorganic species of Hg, yet appear to be more toxic to organ systems. The findings from this study are the first to show that Hg(CN) 2 complexes are highly stable complexes that can lead to cellular injury and death in mammalian organ systems.

The current study examined the effectiveness of glycyrrhizic acid (GA) in reducing cell viability and inducing apoptosis in human chronic myeloid leukemia (CML) in vitro and a mouse lymphoma in vivo. Additionally, we assessed GA as a candidate for combinational therapy in CML along with the current frontline treatment, imatinib (IM). Treatment of K562 CML cells with GA alone resulted in significant induction of apoptosis and loss of cell viability. GA was well tolerated by peripheral blood mononuclear cells (PBMCs) up to 2 mM doses which were subsequently used in combination with IM. Co-treatment of CML with GA and IM greatly enhanced the levels of apoptosis in human CML. The effectiveness of GA was not limited to in vitro studies as treatment of EL-4 lymphoma-bearing mice with GA (50 or 500 mg/kg/day) led to significant dose-related decrease in tumor burden that correlated with a significant increase in the level of apoptotic tumors in vivo. The broad activity of GA against different tumor cell types, its tolerance by PBMCs and synergistic effects when combined with IM suggests that GA may be a viable candidate for combinational treatment strategies in CML and other hematological malignancies., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: As an inhibitor of hyaluronic acid (HA) synthesis, 4-methylumbelliferone (4-MU) has been shown to induce apoptosis of various types of cancer cells. However, the potential impact of 4-MU-induced apoptosis on leukemia cells via modulation of HA is not well-known., Materials and Methods: We examined apoptosis of chronic myelogenous leukemia (CML) cells after treatment with 4-MU using annexin V/propidium iodide (V/PI) analysis and poly (ADP-ribose) polymerase (PARP) cleavage. We further examined the mechanisms of 4-MU-induced apoptosis by measuring mitochondrial membrane potential and reactive oxygen species generation. Using real-time PCR, and western blot analysis we examined signaling pathways involved in apoptosis., Results: The current study demonstrated that treatment of CML cells with 4-MU led to induction of apoptosis through PARP cleavage and loss of mitochondria membrane potential. Mechanistically, 4-MU led to increased p53 mRNA expression, elevated cytoplasmic protein levels of cytochrome c and B-cell lymphoma-2-associated X (BAX) and reduced levels of B-cell lymphoma-2 (BCL2) expression. Addition of exogenous soluble HA was able to protect 4-MU-exposed cells from apoptosis., Conclusion: Our findings suggest that 4-MU induces apoptosis in CML cells by activating components associated with the intrinsic apoptosis pathway., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)