Structure-activity relationship studies of benzothiazole-phenyl analogs as multi-target ligands to alleviate pain without affecting normal behavior.

Soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) are potential targets for several diseases. Previous studies have reported that concomitant selective inhibition of sEH and FAAH produced antinociception effects in an animal model of pain. However, the co-administration of a selective sEH inhibitor and a selective FAAH inhibitor might produce serious side effects due to drug-drug interactions that could complicate drug development in the long term. Thus, discovering dual sEH/FAAH inhibitors, single small molecules that can simultaneously inhibit both sEH and FAAH, would be a significant accomplishment in the medicinal chemistry field. Herein, we report the synthesis and biological evaluation of benzothiazole-phenyl-based analogs as potential dual sEH/FAAH inhibitors. This work represents a follow-up structure-activity relationship (SAR) and metabolic-stability studies of our best dual sEH/FAAH inhibitor identified previously, as well as in vivo evaluation of its effects on voluntary locomotor behavior in rats. Our SAR study indicates that trifluoromethyl groups on the aromatic rings are well tolerated by the targeted enzymes when placed at the ortho and para positions; however, they, surprisingly, did not improve metabolic stability in liver microsomes. Our behavioral studies indicate that doses of dual sEH/FAAH inhibitors that alleviate pain do not depress voluntary behavior in naïve rats, which is a common side effect of currently available analgesic drugs (e.g., opioids). Thus, dual sEH/FAAH inhibitors may be a safe and effective approach to treat pain.

Intentional tanning behaviors among undergraduates on the United States' Gulf Coast.

BACKGROUND: Rates of melanoma have dramatically increased among adolescents and young adults in recent years, particularly among young women. Exposure to ultraviolet radiation from intentional tanning practices is likely a major contributor to this epidemic. Southern and coastal regions have higher melanoma mortality rates among non-Hispanic whites in other parts of the U.S., yet little is known about tanning practices of adolescents and young adults in these regions. This study determines the prevalence and methods of intentional tanning utilized by an undergraduate population located on the United States' Gulf Coast. METHODS: Undergraduate students enrolled at a university on the Gulf Coast completed an online survey from March-April 2016, self-reporting their engagement, knowledge, and attitudes regarding outdoor tanning (OT), indoor tanning (IT) and spray tanning (ST). Univariate and multivariate analyses were performed to identify factors associated with tanning behaviors. RESULTS: 2668 undergraduates completed the survey. Of these, 64.9% reported OT tanning, 50.7% reported ever IT, and 21.2% reported ever ST. CONCLUSIONS: In the largest study to date of intentional tanning behaviors of adolescents and young adults from coastal regions, we found high rates of intentional tanning behaviors. There was also significant engagement in spray tanning by this population, not previously reported for adolescents and young adults in a sample of this size. We also identified a high association between different tanning methods, indicating this population engages in multiple tanning behaviors, a phenomenon whose health consequences are not yet known.

Significant Engagement in Tanning Behaviors by Men at a U.S. University.

Adolescent and young adult men are a potentially overlooked population with respect to risky tanning behaviors. This study sought to determine the prevalence of various modes of tanning and associated variables among young men in a university setting in the southeastern United States. Undergraduate students at a public institution in Mobile, Alabama were surveyed electronically in March 2016. Of the 818 undergraduate men surveyed, over 90% reported tanning behaviors, with 37% reporting engaging in indoor tanning. Additionally, over 25% reported engaging in two or more types of tanning concurrently. These findings indicate that early intervention efforts targeting young men are needed to reduce risky tanning behaviors and associated negative health outcomes.

College tanning behaviors, attitudes, beliefs, and intentions: A systematic review of the literature.

Despite well-established links between exposure to ultraviolet radiation (UVR) and skin cancer, UVR-based tanning behaviors persist among college students. Understanding tanning motivations, perceptions, barriers, and demographic characteristics of this population is critical to modifying these behaviors, but is limited by variability in study design, sample size, and outcomes measured in the current literature. To help clarify the tanning behaviors of this population and provide a concise reference for future studies, this review examines existing reports to determine the comparability of tanning behaviors across multiple U.S. college populations. A systematic review of the literature was performed in July 2016 to identify studies investigating tanning behaviors among U.S. college students. Twenty-three studies met inclusion criteria. High rates of indoor tanning (IT) and outdoor tanning (OT) were found among college students. Key motivators included appearance, emotion, health perceptions, and the influence of parents, peers, and the media. Misconceptions regarding skin protection, low rates of sun protective behaviors, and tanning dependence were barriers against safe UVR exposure. Understudied demographic factors may account for variance in observed tanning behaviors, emphasizing the need for standardization efforts to consistently identify trends associated with geographical region, age, year in college, and sex. The findings presented in this review reaffirm that college students are at high risk for tanning-associated skin cancer, emphasizing the critical need for effective, targeted interventions. Improved interventions will reduce the burden of skin cancer within this group, ultimately contributing to longer, healthier lives.

Mangiferin and Cancer: Mechanisms of Action.

Mangiferin, a bioactive compound derived primarily from Anacardiaceae and Gentianaceae families and found in mangoes and honeybush tea, has been extensively studied for its therapeutic properties. Mangiferin has shown promising chemotherapeutic and chemopreventative potential. This review focuses on the effect of mangiferin on: (1) inflammation, with respect to NFκB, PPARÒ¯ and the immune system; (2) cell cycle, the MAPK pathway G2/M checkpoint; (3) proliferation and metastasis, and implications on ß-catenin, MMPs, EMT, angiogenesis and tumour volume; (4) apoptosis, with a focus on Bax/Bcl ratios, intrinsic/extrinsic apoptotic pathways and telomerase activity; (5) oxidative stress, through Nrf2/ARE signalling, ROS elimination and catalase activity; and (6) efficacy of chemotherapeutic agents, such as oxaliplatin, etoposide and doxorubicin. In addition, the need to enhance the bioavailability and delivery of mangiferin are briefly addressed, as well as the potential for toxicity.