Genome Mining Leads to Diverse Sesquiterpenes with Anti-inflammatory Activity from an Arctic-Derived Fungus.

With the advancement of bioinformatics, the integration of genome mining with efficient separation technology enables the discovery of a greater number of novel bioactive compounds. The deletion of the key gene responsible for triterpene cyclase biosynthesis in the polar strain Eutypella sp. D-1 instigated metabolic shunting, resulting in the activation of dormant genes and the subsequent production of detectable, new compounds. Fifteen sesquiterpenes were isolated from the mutant strain, with eight being new compounds. The structural elucidation of these compounds was obtained through a combination of HRESIMS, NMR spectroscopy, and ECD calculations, revealing six distinct skeleton types. Compound 7 possessed a unique skeleton of 5/10 macrocyclic ether structure. Based on the gene functions and newly acquired secondary metabolites, the metabolic shunting pathway in the mutant strain was inferred. Compounds 6, 8, 11, 14, and 15 exhibited anti-inflammatory effects without cytotoxicity through the release of nitric oxide from lipopolysaccharide-stimulated RAW264.7 cells. Notably, acorane-type sesquiterpene 8 inhibited nitric oxide production and modulated the MAPK and NLRP3/caspase-1 signaling pathways. Compound 8 also alleviated the CuSO4-induced systemic neurological inflammation symptoms in a transgenic fluorescent zebrafish model.

Epimedin B exerts an anti-inflammatory effect by regulating the MAPK/NF-κB/NOD-like receptor signalling pathways.

Epimedin B (EB), a predominant compound found in Herba Epimedii, has been shown to be effective in the treatment of osteoporosis and peripheral neuropathy. However, the anti-inflammatory effect of EB has not yet been reported. The anti-inflammatory activity of EB was evaluated in a zebrafish inflammation model induced by copper sulfate (CuSO4) and tail cutting. Our findings demonstrated that EB effectively inhibited acute inflammation, mitigated the accumulation of reactive oxygen species (ROS), and ameliorated the neuroinflammation-associated impairment of locomotion in zebrafish. Moreover, EB regulates several genes related to the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB)/Nod-like receptor signalling pathways (mapk8b, src, mmp9, akt1, mapk14a, mapk14b, mapk1, egfra, map3k4, nfκb2, iκbαa, pycard, nlrp3 and caspase1) and inflammatory cytokine (stat6, arg1, irfɑ, stat1ɑ, il-1ß, il-4, il-6, il-8, cox-2, ptges, tnf-α and tgf-ß). Therefore, our findings indicate that EB could serve as a promising therapeutic candidate for treating inflammation.

Pimarane-Type Diterpenes with Anti-Inflammatory Activity from Arctic-Derived Fungus Eutypella sp. D-1.

The Arctic-derived fungus Eutypella sp. D-1 can produce numerous secondary metabolites, and some compounds exhibit excellent biological activity. Seven pimarane-type diterpenes, including three new compounds eutypellenone F (1), libertellenone Y (2), and libertellenone Z (3), and four known compounds (4-7), were isolated from fermentation broth of Eutypella sp. D-1 by the OSMAC strategy of adding ethanol as a promoter in the culture medium. Compound 2 has a rare tetrahydrofuran-fused pimarane diterpene skeleton. The anti-inflammatory activity of all compounds was evaluated. Compounds 3-6 showed a significant inhibitory effect on cell NO release at 10 µmol/L by in vitro experiments, of which 3-5 had inhibitory rates over 60% on nitric oxide (NO) release. Subsequently, the anti-inflammatory activity of 3-5 was evaluated based on a zebrafish model, and the results showed that 3 had a significant inhibitory effect on inflammatory cells migration at 40 µmol/L, while 4 and 5 had a significant inhibitory effect at 20 µmol/L. Moreover, compounds 3-5 have the same conjugated double bond structure, which may be an important group for these compounds to exert anti-inflammatory activity.

Examining the incubation period distributions of COVID-19 on Chinese patients with different travel histories.

INTRODUCTION: Current studies estimated a general incubation period distribution of COVID-19 based on early-confirmed cases in Wuhan, and have not examined whether the incubation period distribution varies across population segments with different travel histories. We aimed to examine whether patients infected by community transmission had extended incubation periods than the early generation patients who had direct exposures to Wuhan. METHODOLOGY: Based on 4741 patient case reports from municipal centers of disease control by February 21, 2020, we calculated the incubation periods of 2555 patients with clear epidemiological survey information and illness development timeline. All patients were categorized into five groups by their travel histories. Incubation period distributions were modeled for each group by the method of the posterior Weibull distribution estimation. RESULTS: Adults aged 30 to 59 years had the most substantial proportion of confirmed cases in China. The incubation period distribution varied slightly across patient groups with different travel histories. Patients who regularly lived in Wuhan and left to other locations before January 23, 2020 had the shortest posterior median value of 7.57 days for the incubation period, while the incubation periods for persons affected by local community transmission had the largest posterior median of incubation periods, 9.31 days. CONCLUSIONS: The median incubation period for all patients infected outside Wuhan was 9 days, a bit of more extended than the early estimated 5-day incubation period that was based on patients in Wuhan. Our findings may imply the decreases of virulence of the COVID-19 virus along with intergenerational transmission.