ABSTRACT
Abuse of nitrous oxide leads to irreversible neurologic deficits. Nitrous oxide is commonly abused through the inhalation of whipped cream canisters. These whipped cream chargers, also known as "whippits," are widely available in the United States and their sale is unregulated. There is an increasing prevalence of whippet abuse, and many are unaware of the catastrophic effects. The mechanism of injury is mediated through severe depletion of vitamin B12. Here, we report a case of nitrous oxide abuse leading to thoracic cord myelopathy. The patient has been inhaling approximately 80-100 nitrous oxide canisters daily for three months total. A magnetic resonance imaging (MRI) of the spinal cord illustrates the lesion within the thoracic cord. Further diagnostic workup with serum vitamin B12 levels was normal. However, elevated levels of methylmalonic acid (MMA) were seen. Despite supplementation of vitamin B12, the patient's neurologic deficits persisted, and he was referred to a rehabilitation center. The abuse of whippets is a serious public health threat and warrants greater regulation of their sale. MMA and holotranscobalamin (holoTC) are improved biomarkers for diagnosing vitamin B12 deficiency.
ABSTRACT
Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase 1 (LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.