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The therapeutic effects of saffron have been reported and described in relation to its major derivatives. Among them, in terms of saffron’s properties, crocin and crocetin absorption and bioavailability have been the most studied. Nevertheless, the metabolism of these major compounds of saffron has not yet been entirely elucidated. Current data indicate that the phase 2 metabolism of crocetins go through conjugation reactions. Crocetins could also be present in isomeric forms such as other carotenoids. Nonetheless, there are still shadow areas in regard to the measurements of the different circulating forms of crocetins after oral saffron extract administration (Safr’Inside™). In using various approaches, we propose the identification of a new cis isomeric form of crocetin, the 6-cis-crocetin. This compound was found in human serum samples after an oral administration of saffron extract. The 6-cis-crocetin represents 19% of the total crocetin measured after 45 min of consumption. These data mark, for the first time, the presence of a cis isomeric form of crocetin in human serum samples. Moreover, this study led to the development of an analytical method that is able to identify and quantify both isomeric forms (trans and cis).

Safe and anti-inflammatory plant-based natural products present an increasing focus in the treatment of chronic inflammatory diseases such as osteoarthritis or inflammatory bowel diseases. Among them, saffron, a spice derived from the stigma of Crocus sativus, could have anti-inflammatory properties and would be therefore a promising therapeutic agent for the treatment of such conditions. However, the anti-inflammatory molecular mechanisms of saffron in humans are still understudied and unclear. In this study, combining human serum metabolites and cell cultures, we evaluated the effect of circulating metabolites from the consumption of a patented saffron extract (Safr’InsideTM) on the chondrocytes and colon epithelial cell responses to inflammatory stress. Parametric or non-parametric Analysis of Variance with post hoc tests was performed. We demonstrated that human serum containing metabolites from saffron intake attenuated IL-1β-stimulated production of PGE2 and MMP-13 in chondrocyte cells and limited the increase in ICAM-1, MCP-1, iNOS, and MMP-3 in human epithelial cells following combined IL-1β and TNF-α inflammatory stimulation. Altogether, these data provide new findings into the mechanisms underlying the beneficial effects of saffron on chondrocytes and enterocyte cells at the cellular level and in the context of chronic inflammatory disorders.

Bisphenol S (BPS) affects terminal folliculogenesis by impairing steroidogenesis in granulosa cells from different species. Nevertheless, limited data are available on its effects during basal folliculogenesis. In this study, we evaluate in vitro the effects of a long-term BPS exposure on a model of basal follicular development in a mono-ovulatory species. We cultured ovine preantral follicles (180–240 μm, n = 168) with BPS (0.1 μM (possible human exposure dose) or 10 μM (high dose)) and monitored antrum appearance and follicular survival and growth for 15 days. We measured hormonal secretions (oestradiol (at day 13 [D13]), progesterone and anti-Müllerian hormone [D15]) and expression of key follicular development and redox status genes (D15) in medium and whole follicles, respectively. BPS (0.1 µM) decreased oestradiol secretion compared with the control (−48.8%, p < 0.001), without significantly impairing antrum appearance, follicular survival and growth, anti-Müllerian hormone and progesterone secretion and target gene expression. Thus, BPS could also impair oestradiol secretion during basal folliculogenesis as it is the case during terminal folliculogenesis. It questions the use of BPS as a safe BPA substitute in the human environment. More studies are required to elucidate mechanisms of action of BPS and its effects throughout basal follicular development.

This work shows that the demonstration of Proposition 15 of Germain et al. (2015) is awed and the proposition is false in a general setting. This proposition gave an inequality that upper-bounds the variance of the margin of a weighted majority vote classifier. Even though this aw has little impact on the validity of the other results presented in Germain et al. (2015), correcting it leads to a deeper understanding of the C-bound, which is a key inequality that upper-bounds the risk of a majority vote classifier by the moments of its margin, and to a new result, namely a lower-bound on the C-bound. Notably, Germain et al.'s statement that "the C-bound can be arbitrarily small" is invalid in presence of irreducible error in learning problems with label noise. In this erratum, we pinpoint the mistake present in the demonstration of the said proposition, we give a corrected version of the proposition, and we propose a new theoretical lower bound on the C-bound. [ABSTRACT FROM AUTHOR]

Increases in oxidative stress have been reported to play a central role in the vulnerability to depression, and antidepressant drugs may reduce increased oxidative stress in patients. Among the plants exerting anti-inflammatory and anti-oxidant properties, saffron, a spice derived from the flower of Crocus sativus, is also known for its positive effects on depression, potentially through its SSRI-like properties. However, the molecular mechanisms underlying these effects and their health benefits for humans are currently unclear. Using an original ex vivo clinical approach, we demonstrated for the first time that the circulating human metabolites produced following saffron intake (Safr'InsideTM) protect human neurons from oxidative-stress-induced neurotoxicity by preserving cell viability and increasing BNDF production. In particular, the metabolites significantly stimulated both dopamine and serotonin release. In addition, the saffron's metabolites were also able to protect serotonergic tone by inhibiting the expression of the serotonin transporter SERT and down-regulating serotonin metabolism. Altogether, these data provide new biochemical insights into the mechanisms underlying the beneficial impact of saffron on neuronal viability and activity in humans, in the context of oxidative stress related to depression. [ABSTRACT FROM AUTHOR]

AimWe aimed to describe the characteristics of individuals infected by BA.4 or BA.5 in France in comparison to BA.1, and analyze the factors associated with hospitalization among BA.4 and BA.5 cases.MethodsA standardized questionnaire was used to collect information on confirmed and probable Omicron cases. Hospitalization risk factors among BA.4/BA.5 cases were analyzed using Poisson regression. Variables with a p-value below 0.2 in the univariate analysis and a priori confounders were included in the multivariable regression model.ResultsThe median age of the 301 cases investigated was 47 years and 97% of cases were symptomatic. The most common clinical signs were asthenia/fatigue (75.7%), cough (58.3%), fever (58.3%), headache (52.1%) and rhinorrhea (50.7%). Twelve cases were hospitalized, and 27.1% reported risk factors. No admissions to intensive care and no deaths were reported. Vaccination status was available for 292 cases, 20.9% were unvaccinated, 1.4% had received one dose, 38.3% two doses and 39.4% three doses. Cases presenting at least one risk factor were almost seventeen times more likely to be hospitalized than those with no risk factors (aRR = 16.72 [95% CI2.59–326.86]).ConclusionDespite the longer duration of and the differences in symptoms and their possible immune escape, BA.4/BA.5 Omicron sub-lineages globally showed no severe clinical presentation. The presence of at least one risk factor for severe disease significantly increased the risk of hospitalization for those infected with BA.4 or BA.5.