Notes

Any regional variety of coevolution between Eurosta solidaginis (Fitch) and its number grow extra tall goldenrod Solidago altissima (D.).
Nevertheless, these emerging studies shed light on the role of VCP/p97 and its therapeutic potential in cardiovascular diseases. In other words, VCP/p97 may be involved in the development of cardiovascular disease, and is anticipated to be a new therapeutic target. This review summarizes current findings regarding VCP/p97 in the cardiovascular system for the first time, and discusses the role of VCP/p97 in cardiovascular disease.Although transport into the nucleus mediated by the importin (IMP) α/β1-heterodimer is central to viral infection, small molecule inhibitors of IMPα/β1-dependent nuclear import have only been described and shown to have antiviral activity in the last decade. Their robust antiviral activity is due to the strong reliance of many different viruses, including RNA viruses such as human immunodeficiency virus-1 (HIV-1), dengue (DENV), and Zika (ZIKV), on the IMPα/β1-virus interface. High-throughput compound screens have identified many agents that specifically target this interface. Of these, agents targeting IMPα/β1 directly include the FDA-approved macrocyclic lactone ivermectin, which has documented broad-spectrum activity against a whole range of viruses, including HIV-1, DENV1-4, ZIKV, West Nile virus (WNV), Venezuelan equine encephalitis virus, chikungunya, and most recently, SARS-CoV-2 (COVID-19). Ivermectin has thus far been tested in Phase III human clinical trials for DENV, while there are currently close to 80 trials in progress worldwide for SARS-CoV-2; preliminary results for randomised clinical trials (RCTs) as well as observational/retrospective studies are consistent with ivermectin affording clinical benefit. Agents that target the viral component of the IMPα/β1-virus interface include N-(4-hydroxyphenyl) retinamide (4-HPR), which specifically targets DENV/ZIKV/WNV non-structural protein 5 (NS5). 4-HPR has been shown to be a potent inhibitor of infection by DENV1-4, including in an antibody-dependent enhanced animal challenge model, as well as ZIKV, with Phase II clinical challenge trials planned. The results from rigorous RCTs will help determine the therapeutic potential of the IMPα/β1-virus interface as a target for antiviral development.Licorice (Glycyrrhiza) produces glycyrrhizin, a valuable triterpenoid saponin, which exhibits persistent sweetness and broad pharmacological activities. In the genus Glycyrrhiza, three species, Glycyrrhiza uralensis, Glycyrrhiza glabra and Glycyrrhiza inflata, produce glycyrrhizin as their main triterpenoid saponin, which has a ketone group at C-11. Other Glycyrrhiza species produce mainly oleanane-type saponins, which harbor homoannular or heteroannular diene structures that lack the C-11 ketone. Although the glycyrrhizin biosynthetic pathway has been fully elucidated, the pathway involving saponins with diene structures remains unclear. CYP88D6 from G. uralensis is a key enzyme in glycyrrhizin biosynthesis, catalyzing the sequential two-step oxidation of β-amyrin at position C-11 to produce 11-oxo-β-amyrin. In this study, we evaluated the functions of CYP88D6 homologs from the glycyrrhizin-producing species G. glabra and G. inflata and from the non-glycyrrhizin-producing species Glycyrrhiza pallidiflora and Glycyrrhiza macedonica, using yeast engineered to supply β-amyrin as a substrate. Yeast expressing CYP88D6 homologs from glycyrrhizin-producing species produced 11-oxo-β-amyrin. However, yeast expressing CYP88D6 homologs (such as CYP88D15) from the non-glycyrrhizin-producing Glycyrrhiza species accumulated oleana-9(11),12-dien-3β-ol and oleana-11,13(18)-dien-3β-ol; these diene compounds are non-enzymatic or yeast endogenous enzymatic dehydration derivatives of 11α-hydroxy-β-amyrin, a direct reaction product of CYP88D15. SD49-7 nmr These results suggest that the activities of CYP88D6 homologs, particularly their ability to catalyze the second oxidation, could influence glycyrrhizin productivity and diversify the chemical structures of saponins in Glycyrrhiza plants. A synthetic biological approach to engineer CYP88D15 could enable the production of pharmacologically active saponins with diene structures, such as saikosaponins, whose biosynthetic pathways have yet to be fully characterized.
Diet is associated with the onset of inflammatory bowel disease [IBD]. Up to half of IBD patients believe that diet contributes to flares. However, studies on this topic are sparse and merely focus on specific nutrients, food items or food groups. We aimed to analyse the association between dietary patterns and flare occurrence in two geographically distinct Dutch cohorts.

In this longitudinal study, 724 IBD patients [Northern cohort n = 486, Southern cohort n = 238] were included and followed for 2 years. Habitual dietary intake was obtained via semi-quantitative food frequency questionnaires at baseline. Principal component analysis [PCA] was conducted on 22 food groups to identify dietary patterns. Flare occurrence was analysed in 427 patients in remission at baseline, using multivariable Cox proportional hazards.

Compared to the Southern cohort, patients in the Northern cohort were younger at diagnosis, comprised more females, and had lower overall energy intakes [all p < 0.05]. PCA revealed three dietary patterns explaining 28.8% of the total variance. The most pronounced pattern [explaining 11.6%] was characterized by intake of grain products, oils, potatoes, processed meat, red meat, condiments and sauces, and sugar, cakes and confectionery. Of the 427 patients, 106 [24.8%] developed an exacerbation during follow-up. The above dietary pattern was associated with flare occurrence (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.04-2.18, p = 0.029), as was female sex [HR 1.63, 95% CI 1.04-2.55, p = 0.032].

A dietary pattern, which can be seen as a 'traditional [Dutch]' or "Western' pattern was associated with flare occurrence. Confirmation in prospective studies is needed.
A dietary pattern, which can be seen as a 'traditional [Dutch]' or "Western' pattern was associated with flare occurrence. Confirmation in prospective studies is needed.
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