Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Dendritic Cell-Derived IL-6 Production and Th17 Differentiation.

IL-17-secreting T cells (Th17 cells) play a pathogenic role in multiple autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)-derived cytokines play pivotal roles in promoting the differentiation of naive CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules blocking the key cytokines produced by DCs will be beneficial in MS. In this article, we report that betaine treatment ameliorates MS pathogenesis by inhibiting DC-derived IL-6 production and Th17 differentiation. Using experimental autoimmune encephalomyelitis, a widely used mouse model of MS, we found that, compared with the vehicle-treated group, betaine-treated mice exhibited less severe experimental autoimmune encephalomyelitis symptoms, including lower clinical scores, reduced leukocyte infiltration, and less extensive demyelination in the CNS. Moreover, a significantly lower percentage of Th17 cells, one of the major pathogenic effector cells in MS progression, was observed in the peripheral immune system and in the CNS. Interestingly, in the in vitro Th17-differentiation assay, no significant change in Th17 cells was observed between the vehicle- and betaine-treated groups, whereas in the in vitro DC culture experiment, betaine treatment significantly decreased DC-derived IL-6 production. In the DC-T cell coculture experiment, a significantly decreased Th17 differentiation was observed upon betaine treatment. All of these data demonstrated that betaine inhibited Th17 differentiation indirectly by reducing IL-6 production by DCs. In brief, our findings demonstrated the pivotal roles of betaine in modulating MS pathogenesis and suggested that it may serve as a potential novel drug candidate for the treatment of MS.

Interannual variation and sources identification of heavy metals in seawater near shipping lanes: Evidence from a coral record from the northern South China Sea.

Heavy metal pollution is a serious environmental problem in the marine ecosystem. Thereinto, marine transportation activities have gradually become an important source of heavy metals in seawater. However, the lack of studies on the temporal dynamics of seawater heavy metals in marine shipping areas has hindered our understanding of the sources and transport mechanisms of heavy metals in seawater of hectic shipping waters. Therefore, we investigated the interannual resolution variation of heavy metals in Porites lutea skeletons during the past 32 years under the rapid development of the shipping sector near Weizhou Island from the northern South China Sea. Results show that most heavy metal concentrations with higher coefficients of variation (≥100 %) in the Porites coral skeletons were higher than those in the uncontaminated or less anthropogenic waters. The results of principal component analysis and multiple linear regression showed that the interannual variations of Ni, V, Cr, Co, Zn, Cu, Mn, Fe and Mo were mainly impacted by marine oil extraction and oil spills generated by shipping activities, accounting for 51.58 %. The effect of sea surface temperature accounts for 13.44 %, and controls the interannual variations of Ba and Sr. The effect of industrial pollution accounts for 13.27 %, and explains the interannual variations of Cd and Y. The fuel consumption of marine shipping accounted for 8.76 %, explaining the interannual variations of Pb. The total contribution of anthropogenic activities reached 73.61 %. The interannual variation of heavy metals indicates that hectic marine shipping activities are the dominant cause of Ni, V, Pb, Cr, Co, Zn, Cu, Mn, Fe and Mo input to surface seawater around Weizhou Island. This provided valuable data for understanding the temporal dynamics and potential sources of heavy metals in the marine environment by using coral skeletons as a high-resolution recording vehicle.

Coral skeletons reveal the impacts of oil pollution on seawater chemistry in the northern South China Sea.

Oil pollution can release trace metals (TMs) with cumulative toxicity into seawater, harming marine ecosystems in the long term. However, the lack of studies has inhibited our understanding of the effects and mechanisms of oil pollution on TMs in seawater. Hence, we investigated the 10-year monthly variation of TMs in Porites coral skeletons from the northern South China Sea (SCS), complemented by spatial distribution of TMs in seawater, sediments and characterization of TMs in fuel oil. The results of principal component-multivariate linear regression showed that the total contribution of oil pollution as a source to TMs in surface seawater was 77.2%, where the residence time of TMs (Ni, V, Cr, Co, Cu, Mn, Fe, and Mo) released from oil spills in surface seawater was approximately 1.4 months. Due to the geochemical nature of the metals, their seasonal variations are controlled by tropical cyclones (Ni, V, Cr, Co, Cu, Mn, Fe, and Mo), winter monsoons (Pb, Cd, Ba, and Zn) and sea surface temperature (Sr). This study shows that coral skeletons can be used as a new tool to study marine oil pollution. This provides valuable reference data for accurately identifying and quantifying the effects of oil pollution on TMs in seawater from a spatial and temporal perspective.

Coral-inferred historical changes of nickel emissions related to industrial and transportation activities in the Beibu Gulf, northern South China Sea.

As one of the most abundant metals in heavy oils, Ni has suffered so notably increasing impacts from industrial and traffic activities that anthropogenic Ni emissions have altered natural geochemical processes. The coral Ni/Ca has become a reliable proxy for characterizing marine pollution, but this potential has been unexploited for highlighting oil pollution. Here, we utilized a high-resolution record of geochemical parameters (Ni/Ca, δ18O, and δ13C) in a Porites coral of an offshore island in the northern South China Sea to reconstruct of Ni distribution patterns in surface seawater from 1984 to 2015. The coral Ni/Ca ratios exhibit minor fluctuations, except for multiple mutation peaks (0.20 ± 0.42 µmol/mol) during the period from 1984 to 1993. The ratio was low and stable (0.10 ± 0.09 µmol/mol) from 1994 to 2008, and then increased rapidly with significant variations (1.60 ± 4.56 µmol/mol) from 2009 to 2015. The coral Ni/Ca ratios captured all significant Ni discharges, and this demonstrates its potential for recording oil spill episodes. The historical variations in the contributions of Ni indicate that industrial and traffic activities should be responsible for changes in the anthropogenic input. The leaks and consumptions of petroleum likely account for the primary Ni emission sources.

Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening.

Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs' cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1ß during the DCs differentiation and maturation. The mechanism studies showed that BVDU treatment restricted the phosphorylation of MAP kinase, which played an important role in DC cytokine production. We further assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly lower EAE clinical scores, decreased leukocyte infiltration in central nervous system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also showed promising therapeutic effects based on both alleviated disease symptoms and tissue pathogenesis. More interestingly, the modulating effect of BVDU on IL-6 production was further verified in human primary DCs. The above data supported the promising application of our screen model, and also the potential of BVDU for autoimmune diseases therapy.