Preeclampsia (PE) is a human pregnancy-specific syndrome with abnormal activation of cells from the innate immune system. The present study evaluated whether silibinin (SB) treatment of monocytes ...from preeclamptic women could modulate NLRP1 and NLRP3 inflammasomes as well as TLR4/NF-κB pathway activation. Peripheral blood monocytes from 20 preeclamptic and 20 normotensive (NT) pregnant women, as well as the THP-1 cell line, were cultured with or without monosodium urate (MSU) or SB.
,
,
,
,
,
,
,
,
and
gene expression by monocytes was analysed by quantitative real-time polymerase chain reaction (qPCR), while inflammatory cytokine production and p65NF-κB activity were determined by enzyme-linked immunosorbent assays (ELISAs). TLR4/MyD88/NF-κB and NLRP1/NLRP3 inflammasomes pathways in THP-1 cells were evaluated by flow cytometry and western blot respectively. Compared with NT women, monocytes from preeclamptic women showed The Ethics Committee of the Botucatu Medical School approved the study (protocol number 2.333.216)higher endogenous activation of NLRP1/NLRP3 inflammasomes and the TLR4/NF-κB pathway as well as higher gene and protein expression of IL-1β, IL-18 and TNF-α, and lower expression of IL-10. Monocyte stimulation with MSU increased inflammation-related genes as well as NF-κB activity. In vitro, SB treatment of monocytes from preeclamptic women reduced the basal activation of these cells by decreasing NLRP1/NLRP3 inflammasomes and p65NF-κB activity. THP-1 cells exhibited a similar immunological response profile to monocytes from preeclamptic women when cultured with or without MSU or SB. These results suggest uric acid participates in the systemic inflammatory response characteristic of preeclampsia and that in vitro SB treatment can modulate the sterile inflammation established in monocytes from preeclamptic women.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Natural molecules, such as flavonoid, are very welcome strategies to modulate bone turnover. This prompted us to comprehend better the effect of silibinin on osteoblast metabolism, mainly considering ...intracellular pathways able to drive cell adhesion to differentiation. By exploring in vitro approaches, our data show a modulatory effect of the silibinin (200 μg/mL) on the osteoblast intracellular signaling, contributing with decisive pathways governing cell adhesion, differentiation, and further mineralization, recapitulating important stages of osteogenesis. Within the first 24 hours of adhesion (acute stage), osteoblasts respond to silibinin by rearranging their cytoskeleton and start mechanisms responsible to extracellular matrix (ECM) remodeling, which reach intense profile at 28 days of treatment (chronic stage) by favoring matrix metalloproteinases (MMPs‐2, and ‐9) activities, concomitant to mineralizing phenotype. Importantly, silibinin seems to reprogram genes related to inflammatory landscape and significantly upmodulating osteoprotegerin (>25 fold‐changes), signaling molecule involved with osteoclastogenesis. Altogether, our results show for the first time that silibinin drives in vitro osteoblast differentiation by requiring specific intracellular signaling. In conjunction, this molecular landscape contributes to understand the effect of silibinin on osteoblasts performance and open novel therapeutic possibilities to silibinin in bone disorders, such as osteoporosis.
Silibinin promotes osteoblast differentiation by requiring cytoskeleton rearrangement as a pre‐requisite to ECM remodeling
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Preeclampsia (PE) is a pregnancy-specific syndrome characterized by a systemic inflammatory response that polarizes peripheral blood monocytes to the M1 phenotype. The classically activated M1 ...monocytes comprise immune effector cells with an acute inflammatory phenotype. CD163 is a scavenger receptor expressed by monocytes/macrophages that may be shed from their cell membrane after proteolytic cleavage, producing the soluble CD163 molecule (sCD163). This study evaluated CD163 expression by monocytes and sCD163 as well as pro- and anti-inflammatory cytokine concentration in the plasma of pregnant women with PE. Fifty-six women with PE and 28 normotensive pregnant women were included. Plasma levels of sCD163, interleukin-1 beta (IL-1β), IL-6, IL-10, transforming growth factor beta (TGF-β1), and tumor necrosis factor-alpha (TNF-α) were determined by ELISA, and CD163 expression by monocytes was assessed by flow cytometry. The expression of CD163 by monocytes was significantly lower in severe and mild PE than in normotensive pregnant. Plasma concentrations of IL-1β, TGF-β1, and TNF-α were higher in severe PE than in mild PE and normotensive pregnant women. Both groups of preeclamptic women showed decreased plasma levels of sCD163 and IL-10. Negative correlations between sCD163 and IL-1β (
r
= − 0.45;
P
= 0.014) and between sCD163 and TNF-α concentrations (
r
= − 0.54;
P
= 0.001) were observed in the severe PE group. The association between the pro-inflammatory cytokine profile and lower concentrations of sCD163 and IL-10 in plasma from women with severe PE suggests an impairment in the modulation of the systemic inflammatory response in this group of pregnant women with preeclampsia.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The oral cavity is a propitious environment for bacteria with different tissue tropisms to colonize and grow due to its diverse surfaces. For bacterial survival in the oral cavity, where tissues are ...continuously bathed in fluids, biofilm formation is necessary. Dental biofilm, i.e. dental plaque, is notoriously hard to inhibit and traditional oral care solutions are either ineffective at managing oral biofilms or cause secondary effects, such as teeth staining, that make them unattractive.
Chitosan has high biocompatibility and antimicrobial activity that is heralded by the pharmaceutical industry for its applicability in biofabrication. Therefore, this material is a potential substitute for the antimicrobials traditionally used in oral care.
Currently, the body of work on chitosan and the oral cavity ranges from planktonic studies in vitro to biofilm control/removal studies in vivo. With a wide range of topics available for analysis, this review provides a working understanding of chitosan's role in the control and management of oral biofilms.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Increased TLR4 expression and NF-κB activation in monocytes from preeclamptic women.•Monocytes activation in preeclampsia may depend on elevated plasmatic danger signals.•LPS tolerance may be ...directly related to the higher DAMPs levels in the plasma.•Cytokine imbalance between normotensive and preeclamptic pregnant women.•Preeclamptic women monocytes show lower activation after stimulation with LPS.
Preeclampsia (PE) is a pregnancy syndrome characterized by a systemic inflammatory response, and endogenous activation of monocytes. This study aimed to determine whether the activation of monocytes from preeclamptic women might interfere with the response to lipopolysaccharide (LPS)-in vitro stimulation. Fifty-two preeclamptic women and 32 normotensive (NT) pregnant women were included. Monocytes from peripheral blood were cultured with or without LPS. TLR4 expression was analyzed by flow cytometry, NF-κB activity was determined in nuclear extracts and cytokines production was evaluated by ELISA. Endogenous TLR4 ligands such as Hyaluronan, HMGB1 and Hsp70 were determined in plasma. The endogenous TLR4 expression and activation of NF-κB were statistically higher in monocytes from women with PE compared to NT group. Early-onset PE showed higher TLR4 expression compared to late-onset PE. Plasma levels of Hyaluronan, HMGB1, and Hsp70, as well as endogenous production of inflammatory cytokines, were elevated whilst lower production of IL-10 was observed in the PE group. After culture with LPS, monocytes presented lower NF-κB activation, TNF-α and IL-12 production in PE groups than in the NT group. The study demonstrates endogenous activation of monocytes from preeclamptic women, accompanied by higher expression of TLR4, NF-κB activation and elevated production of pro-inflammatory cytokines. The higher plasma levels of the TLR4 ligands hyaluronan, HMGB1 and hsp70, as well as the high concentration of TNF-α endogenously produced by monocytes, could induce the LPS tolerance phenomenon in these cells. These results suggest that monocytes play an important role in the maternal excessive systemic inflammatory response in PE.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The phytocannabinoid cannabidiol (CBD) is receiving increasing attention due to its pharmacological properties. Although CBD is extracted from
, it lacks the psychoactive effects of ...Δ9-tetrahydrocannabinol (THC) and has become an attractive compound for pharmacological uses due to its anti-inflammatory, antioxidant, anticonvulsant, and anxiolytic potential. The molecular mechanisms involved in CBD's biological effects are not limited to its interaction with classical cannabinoid receptors, exerting anti-inflammatory or pain-relief effects. Several pieces of evidence demonstrate that CBD interacts with other receptors and cellular signaling cascades, which further support CBD's therapeutic potential beyond pain management. In this review, we take a closer look at the molecular mechanisms of CBD and its potential therapeutic application in the context of cancer, neurodegeneration, and autoimmune diseases.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are ...characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman’s or Pearson’s tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = −0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies.
Cannabidiol (CBD) and cannabigerol (CBG) are two pharmacologically active phytocannabinoids of
L. Their antimicrobial activity needs further elucidation, particularly for CBG, as reports on this ...cannabinoid are scarce. We investigated CBD and CBG's antimicrobial potential, including their ability to inhibit the formation and cause the removal of biofilms. Our results demonstrate that both molecules present activity against planktonic bacteria and biofilms, with both cannabinoids removing mature biofilms at concentrations below the determined minimum inhibitory concentrations. We report for the first time minimum inhibitory and lethal concentrations for
and
(ranging from 400 to 3180 µM), as well as the ability of cannabinoids to inhibit
adhesion to keratinocytes, with CBG demonstrating higher activity than CBD. The value of these molecules as preservative ingredients for cosmetics was also assayed, with CBG meeting the USP 51 challenge test criteria for antimicrobial effectiveness. Further, the exact formulation showed no negative impact on skin microbiota. Our results suggest that phytocannabinoids can be promising topical antimicrobial agents when searching for novel therapeutic candidates for different skin conditions. Additional research is needed to clarify phytocannabinoids' mechanisms of action, aiming to develop practical applications in dermatological use.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Intravenous magnesium sulfate modulates systemic inflammation in severe preeclampsia.•The MgSO4 reduces inflammatory process in imminent eclampsia.•Therapy with MgSO4 decreases production of ...inflammatory mediators in preeclampsia.•Magnesium sulfate up-regulates anti-inflammatory mediators in preeclampsia.•The maintenance dose of MgSO4 at 2 g/hour plays immunomodulatory role in preeclampsia.
This study compared the modulatory effect of two intravenous magnesium sulfate (MgSO4) regimens on the systemic inflammatory response in pregnant women diagnosed with imminent eclampsia.
In a single-blind cross-sectional study, 33 women were allocated according to the Zuspan (n = 16) and Sibai (n = 17) MgSO4 regimens, and treated for 24 h. Blood samples were collected pre-administration of the loading dose, at 24 h of the maintenance dose of MgSO4, and at 48 h, when patients were without treatment. Plasma was used to determine interleukin (IL)-1 beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), heat shock protein (Hsp70), and heme oxygenase-1 (HO-1) by ELISA.
The treatment with the Zuspan’s regimen didn’t change plasma concentrations of TNF-α, IL-10, and Hsp70 in the three-time points studied. However, it decreased IL-1β at 24 h and 48 h and IL-6 at 48 h, and increased HO-1 concentration at 48 h. On the other hand, compared to the pre-treatment period, Sibai’s regimen induced a significant decrease in TNF-α, IL-1β, IL-6, and Hsp70, while increased HO-1 levels both at 24 h and 48 h and, IL-10 concentration at 48 h.
Sibai’s regimen determined an early and efficient immunoregulatory effect on systemic inflammatory response in preeclampsia, suggesting that the maintenance dose of two grams of MgSO4 was better than one gram in the treatment of imminent eclampsia.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nowadays, the agro-food industry generates high amounts of byproducts that may possess added value compounds with high functionality and/or bioactivity. Additionally, consumers' demand for healthier ...foodstuffs has increased over the last years, and thus the food industry has strived to answer this challenge. Byproducts are generally secondary products derived from primary agro-food production processes and represent an interesting and cheaper source of potentially functional ingredients, such as peptides, carotenoids, and phenolic compounds, thus promoting a circular economy concept. The existing body of work has shown that byproducts and their extracts may be successfully incorporated into foodstuffs, for instance, phenolic compounds from eggplant can be potentially used as a mulfitunctional food additive with antimicrobial, antioxidant, and food colorant properties. As such, the aim of this review is to provide insights into byproducts and their potential as new sources of foodstuffs additives.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
