Six new compounds, aristoloxazine A (1), aristoloxazine B (2), 7-methoxytaliscanine (3), humul-7-en-1,4,11-triol (4), 8-hydroxy-β-logipinene (5), and 1β-hydroxy-4(14)-eudesmene (6), corresponding to two sulfur-containing aristoloxazines (1 and 2), an aristolactam (3), and three sesquiterpenes (4-6) were isolated, along with 26 known compounds, from the roots of Aristolochia orbicularis. The structures of the new compounds were established based on their spectroscopic and spectrometric data and in the case of aristoloxazine A (1) by single-crystal X-ray crystallography. This is the first report of sulfur-containing aristoloxazines from a natural source. Furthermore, aristoloxazine A (1) was found to possess potent in vitro antimicrobial activity against all resistant Staphylococcus aureus and several fungal strains in which it was evaluated.

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain “maternal-fetal tolerance”, SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.

Acute systemic inflammation can lead to life-threatening organ dysfunction. In patients with sepsis, systemic inflammation is triggered in response to infection, but in other patients, a systemic inflammatory response syndrome (SIRS) is triggered by non-infectious events. IL-6 is a major mediator of inflammation, including systemic inflammatory responses. In homeostatic conditions, when IL-6 engages its membrane-bound receptor on myeloid cells, it promotes pro-inflammatory cytokine production, phagocytosis and cell migration. However, under non-physiologic conditions, such as SIRS and sepsis, leucocyte dysfunction could modify the response of these cells to IL-6. So, our aim was to evaluate the response to IL-6 of monocytes from patients diagnosed with SIRS or sepsis. We observed that monocytes from patients with SIRS, but not from patients with sepsis, produced significantly more TNF-α than monocytes from healthy volunteers, after stimulation with IL-6. Monocytes from SIRS patients had a significantly increased baseline phosphorylation of the p65 subunit of NF-κB, with no differences in STAT3 phosphorylation or SOCS3 levels, compared to monocytes from septic patients, and this increased phosphorylation was maintained during the IL-6 activation. We found no significant differences in the expression levels of the membrane-bound IL-6 receptor, or the serum levels of IL-6, soluble IL-6 receptor, or soluble gp130, between patients with SIRS and patients with sepsis. Our results suggest that, during systemic inflammation in the absence of infection, IL-6 promotes TNF-α production by activating NF-κB, and not the canonical STAT3 pathway.

On January 30th, 2020, the WHO declared the outbreak of COVID19, a disease due to the new coronavirus called SARS-CoV-2. Certain comorbidities, symptoms and signs are characteristic of COVID19 in the general population and in pregnant women. However, pregnant women are considered as a high-risk group for COVID19. To know about the frequency of comorbidities, signs and symptoms, the presence of lymphopenia, antibodies response to SARS-CoV2 and cytokine and chemokine serum concentration, six pregnant women with COVID19 were studied at the moment of admission. The lower concentration of CCL17 was detected in the Pregnant COVID19 group, similar concentration of IL-6 was also detected in non-pregnant and pregnant COVID19 patients. Our result show that pregnant and non-pregnant women with COVID19 has similar cytokine profile.