Anti-Caffeine monoclonal antibody

Zeatin, an adenine-derivative cytokinin has well-established functions in plants. It is also suggested to activate A2A receptors in animals, however, there is limited knowledge of its effects. The main objective of this study is to evaluate the possible effects of zeatin on depression, and our hypothesis is that zeatin might induce an antidepressant effect via A2A receptor-linked pathways. The forced swim test was used to create a depression-like model on female and male rats. A balanced zeatin isomer mixture (80 % trans-zeatin (tZ), 20 % cis-zeatin (cZ)) was administered intraperitoneally to analyze the effects. Caffeine with a suboptimal dose (2 mg/kg) was used as a known ligand of A2A receptor. Finally, a molecular docking study was also implemented to compare caffeine and tZ in the ligand binding site of A2A receptor. We demonstrate that (1) there is a clear sex-dependent difference in the susceptibility to depression-like symptoms, where female rats in the metestrus phase display higher depressive-like behavior and lower responses to the anti-depressant-like effects of pharmacological applications; (2) 10 mg/kg zeatin exerts an anti-depressant-like effect for both females and males without affecting locomotor activity; (3) 8 mg/kg tZ alone replicates this effect for both sexes, (4) the effect of zeatin is also differential for either sex and (5) the similar effect of caffeine and zeatin implies that the effect might be exerted via A2A receptor mediated pathways. Computational analysis further yielded similar binding patterns for both ligands. In conclusion, zeatin might have a potential therapeutic use in depression, acting via adenosinergic pathways.

Background Epidemiological data suggest that coffee has a dose-dependent protective effect on liver-related mortality. Aim To estimate the potential impact of increased per capita coffee consumption on global liver-related mortality. Methods Using the Global Burden of Disease 2016 dataset (adults > 15 years), we modelled the impact of increased per capita coffee consumption on liver-related mortality in 2016 for 194 countries using published risk ratios for >2 cups coffee/ day (RR 0.54, 95% CI 0.42-0.69) and >= 4 cups/ day (RR 0.29, 95% CI 0.17-0.50), adjusted for confounders and tested model assumptions using sensitivity analyses. Results Worldwide, there were an estimated 1,240,201 (95% CI 118 4300-1 354 410) adult liver-related deaths in 2016. Median global liver mortality rate in 2016 was 15 deaths/ 100 000 population/ year (all ages, both genders; IQR 11-21 deaths per 100 000). If all countries with per capita coffee intake <= 2 cups/ day increased to >2 cups/ day, the predicted total number of liver-related deaths would have been 630 947 in 2016 (95% CI 629 693-631 861) with 452 861 (95% CI 451 948-454 116) deaths averted (PPR 7.8 liver-related deaths/ 100 000/ year). If per capita consumptions was >= 4 cups/ day, the predicted number of liver-related deaths in 2016 would have been 360 523 (95% CI 359 825-361 992) with 723 287 (95% CI 721 817-723 984) deaths averted (PPR 12.1 liver-related deaths/100 000/year). Conclusion Increasing per capita coffee consumption to > 2 cups per day on a population level has the potential to avert hundreds of thousands of liver-related deaths annually if the impact of coffee on liver-related mortality is confirmed in clinical trials.