Institute for EthnoMedicine

Many herbivorous Lepidoptera accumulate plant toxins within their own tissues as a defensive strategy. Pioneering research in this area was conducted by Miriam Rothschild and Deane Bowers, who showed that the cycad-feeding butterfly Eumaeus atala sequester the toxic plant compound cycasin and thereby deter vertebrate and invertebrate predators. The current study focuses on another cycad compound, β-methylamino-L-alanine (BMAA), that is known to accumulate in the tissues of insects and other herbivores, and which has been shown to have neurotoxic effects in humans. Chemical analyses revealed that BMAA accumulates in both immature and adult tissues of E. atala, as well as adult tissues of another cycad-feeding lepidopteran, Seirarctia echo. However, the distribution of BMAA across life stages and tissues did not conform to patterns predicted for defensive sequestration, and subsequent behavioral experiments with ants showed that these invertebrate predators were not deterred by BMAA. Our results suggest that high levels of BMAA in the tissues of cycad-feeding insects likely reflect passive bioaccumulation rather than defensive sequestration. Combined with the previous work by Rothschild and Bowers, these results provide an example in which two different plant toxins accumulate within the tissues of a single herbivore species via different mechanisms and with different implications for ecology and evolution. They thereby lay the groundwork for further investigation into the processes underlying active sequestration and non-adaptive bioaccumulation.

Genistein is one of the main components of soybeans and has been reported to be a potential candidate for the treatment of obesity, cancer, osteoporosis and cardiovascular diseases. Recently, genistein has been shown to have therapeutic effects on some chronic skin diseases, but its underlying mechanisms remain unclear. In this study, we evaluated the role of genistein in alleviating squaric acid dibutylester (SADBE)-induced allergic contact dermatitis (ACD) in mice, and elucidated the potential molecular mechanisms in human keratinocyte (HaCaT) cell line. The impacts of genistein on the production of pro-inflammatory chemokines and cytokines including CXCL9, TSLP, TNF-α, IL-1β and IL-6 in the skin and serum of ACD mice were assessed, as well as the phosphorylation of components in the MAPK and JAK-STAT3 signaling pathways in the skin and dorsal root ganglions (DRGs). The results showed that genistein exerted protective effects on skin damage and inflammatory cell infiltration. Moreover, genistein significantly inhibited the increased expressions of pro-inflammatory factors in skin and peripheral blood, and down-regulated the levels of p-ERK, p-p38 and p-STAT3 in skin and DRGs. Furthermore, genistein inhibited the phosphorylation of ERK and STAT3 to downregulate the expression of cytokines and chemokines, and feedback downregulate phospho-p38 in TNF-α/IFN-γ-induced HaCaT cells. The genistein-mediated inhibitory effect on the MAPK pathway can be reversed by siMAP2K2 but not by siMAP2K4. Altogether, our findings demonstrated that genistein exhibits strong antipruritic and anti-inflammatory effects in ACD mice by inhibiting the production of pro-inflammatory cytokines and intracellular MAP2K2/ERK cell signaling, which makes genistein a potentially valuable candidate for the treatment of skin conditions and systemic syndromes in the setting of contact dermatitis.

Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer's, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk.

In this study, we proposed a metabolomics strategy to distinguish different metabolic characters of healthy controls, breast benign (BE) patients, and breast malignant (BC) patients by using the GC-MS and random forest method (RF).

One Health is the combination of multidisciplinary efforts and expertise from the fields of medicine and science to determine environmental factors that affect human, animal, plant and microbial health in natural and built environments. The One Health initiative has gained momentum in recent decades, yet it has its roots of inception at the beginning of Western medicine when Hippocrates realized that human and ecosystem health are intrinsically connected and should not be considered in isolation.Our studies focus on cyanobacteria and how their abundance and toxin production are affected by unique climatological attributes of the desert, as well as anthropogenic influences and practices. We have determined that cyanobacterial crusts and mats can cover up to 87% of the terrestrial and coastal surface of Qatar, contributing to ecosystem health by preventing soil and coastal sediment erosion and enhancing rain water retention allowing for plant proliferation.Cyanobacteria negatively impact human and ecosystem health through the production of a range of toxins known or suspected to produce liver damage, promote tumors, cause paralysis, and potentially trigger neurodegenerative disease in humans and other animals. We have discovered that toxin-producing cyanobacterial species and cyanotoxins are present in both terrestrial crusts and coastal mats of Qatar.In the current paper, we present our results on cyanotoxin transmission and exposure routes to humans through air, drinking water and foodstuffs. We have observed that the annual natural phenomenon of dust storms experienced in the Arabian Peninsula leads to airborne cyanobacteria and cyanotoxins, and that in areas impacted by anthropogenic infrastructure development there is an increased rate of airborne exposure. Interestingly, local dress of gutras and sheilas act as natural filters against inhalation, minimizing exposure to cyanobacterial cells and cyanotoxins in controlled lab experiments.Another feature unique to desert life is the transportation and storage of desalinated water, kept in impoundments for drinking. We have tested water contained in such tanks in both rural and urban desert settings. Visible growth of cyanobacteria was observed in the majority of the tanks, with the neurotoxin AEG present in 90% of rural tanks, and 30% of urban tanks had concentrations of the hepatotoxin microcystin exceeding the World Health Organization’s Provisional Guideline value for lifetime health protection.Finally, we have performed biomagnification studies in the marine food chain of the gulf, choosing marine species based on consumer preferences of the local population.Neurotoxins were found in marine species at all trophic levels, attributed to the bottom up influence of toxins present in cyanobacterial mats or to top down effects of localized cyanobacterial blooms potentially caused by discharge of ballast water into the gulf.Our studies have shed the light on an unexplored biological desert system. Our findings may be used for conservation of this vital biota and for improving the design of built environments, construction procedures and water transportation and storage practices to minimize human exposure to cyanobacteria and their toxins through air and water.