Healthberry 865® and a Subset of Its Single Anthocyanins Attenuate Oxidative Stress in Human Endothelial In Vitro Models
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ABSTRACT:
SUBMITTER: Ockermann P
PROVIDER: S-EPMC9325219 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In recent years, epidemiological studies have identified a relationship between diet and cerebro-cardiovascular disease (CVD). In this regard, there is a promising dietary group for cardiovascular protection are polyphenols, especially anthocyanins. Vascular reactivity studies were performed using Healthberry 865® and constituent single anthocyanins to characterize vasomotor responses; immunofluorescence analysis with dichlorofluorescein diacetate and dihydroethidium were used to evaluate nitric oxide and oxidative stress; lucigenin assay was used to measure NADPH oxidase activity; and gel electrophoresis and immunoblotting were used to dissect the molecular mechanisms involved. We demonstrated that Healthberry 865® exerts an important vasorelaxant effect of resistance artery functions in mice. Its action is mediated by nitric oxide release through the intracellular signaling PI3K/Akt. Moreover, behind its capability of modulating vascular tone, it also exerts an important antioxidant effect though the modulation of the NADPH oxidase enzyme. Interestingly, its cardiovascular properties are mediated by the selective action of different anthocyanins. Finally, the exposure of human dysfunctional vessels to Healthberry 865® significantly reduces oxidative stress and improves NO bioavailability. Although further investigations are needed, our data demonstrate the direct role of Healthberry 865® on the modulation of vasculature, both on the vasorelaxation and on oxidative stress; thus, supporting the concept that a pure mixture of anthocyanins could be helpful in preventing the onset of vascular dysfunction associated with the development of CVD.
| S-EPMC8388872 | biostudies-literature
Project description:Endothelial dysfunction is one of the main age-related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial dysfunction results from decreased bioavailability of nitric oxide (NO) arising downstream of endothelial oxidative stress. In this study, we investigated the protective effect of anthocyanins and the underlying mechanism in rat thoracic aorta and human vascular endothelial cells in aging models. In vitro, cyanidin-3-rutinoside (C-3-R) and cyanidin-3-glucoside (C-3-G) inhibited the d-galactose (d-gal)-induced senescence in human endothelial cells, as indicated by reduced senescence-associated-β-galactosidase activity, p21, and p16INK4a . Anthocyanins blocked d-gal-induced reactive oxygen species (ROS) formation and NADPH oxidase activity. Anthocyanins reversed d-gal-mediated inhibition of endothelial nitric oxide synthase (eNOS) serine phosphorylation and SIRT1 expression, recovering NO level in endothelial cells. Also, SIRT1-mediated eNOS deacetylation was shown to be involved in anthocyanin-enhanced eNOS activity. In vivo, anthocyanin-rich mulberry extract was administered to aging rats for 8 weeks. In vivo, mulberry extract alleviated endothelial senescence and oxidative stress in the aorta of aging rats. Consistently, mulberry extract also raised serum NO levels, increased phosphorylation of eNOS, increased SIRT1 expression, and reduced nitrotyrosine in aortas. The eNOS acetylation was higher in the aging group and was restored by mulberry extract treatment. Similarly, SIRT1 level associated with eNOS decreased in the aging group and was restored in aging plus mulberry group. These findings indicate that anthocyanins protect against endothelial senescence through enhanced NO bioavailability by regulating ROS formation and reducing eNOS uncoupling.
| S-EPMC7744959 | biostudies-literature
Project description:Epileptic seizures are widely regarded to occur as a result of the excitation-inhibition imbalance from a neuro-centric view. Although astrocyte-neuron interactions are increasingly recognized in seizure, elementary questions about the causal role of astrocytes in seizure remain unanswered. Here we show that optogenetic activation of channelrhodopsin-2-expressing astrocytes effectively attenuates neocortical seizures in rodent models. This anti-seizure effect is independent from classical calcium signaling, and instead related to astrocytic Na+-K+-ATPase-mediated buffering K+, which activity-dependently inhibits firing in highly active pyramidal neurons during seizure. Compared with inhibition of pyramidal neurons, astrocyte stimulation exhibits anti-seizure effects with several advantages, including a wider therapeutic window, large-space efficacy, and minimal side effects. Finally, optogenetic-driven astrocytic Na+-K+-ATPase shows promising therapeutic effects in a chronic focal cortical dysplasia epilepsy model. Together, we uncover a promising anti-seizure strategy with optogenetic control of astrocytic Na+-K+-ATPase activity, providing alternative ideas and a potential target for the treatment of intractable epilepsy.
| S-EPMC9681834 | biostudies-literature
Project description:BackgroundAerosol therapy in young children can be difficult. A realistic model based on handling studies and in vitro investigations can complement clinical deposition studies and be used to enable dose-to-the-lung (DTL) predictions.MethodsPredictions on dose delivery to the lung were based on (1) representative inhalation flow profiles from children enrolled in a Respimat® handling study, (2) in vitro measurement of the fine-particle DTL using mouth-throat models derived from nuclear magnetic resonance/computed tomography (NMR/CT) scans of children, and (3) a mathematical model to predict the tiotropium DTL. Accuracy of the prediction was confirmed using pharmacokinetic (PK) data from children with cystic fibrosis enrolled in a phase 3 clinical trial of tiotropium Respimat with valved holding chamber (VHC).ResultsRepresentative inhalation flow profiles for each age group were obtained from 56 children who successfully inhaled a volume >0.15 L from the Respimat with VHC. Average dimensions of the mouth-throat region for 38 children aged 1-<2 years, 2-<3 years, 3-<4 years, and 4-<5 years were determined from NMR/CT scans. The DTL from the Respimat plus VHC were determined by in vitro measurement and were 5.1±1.1%, 15.6%±1.4%, 17.9%±1.5%, and 37.1%±1.8% of the delivered dose for child models 0-<2 years, 2-<3 years, 3-<4 years, and 4-<5 years, respectively. This provides a possible explanation for the age dependence of clinical PK data obtained from the phase 3 tiotropium trial. Calculated in vitro DTL per body mass (μg/kg [±SD]) were 0.031±0.014, 0.066±0.031, 0.058±0.024, and 0.059±0.029, respectively, compared to 0.046 in adults. Therefore, efficacy of the treatment was not negatively impacted in spite of the seemingly low percentages of the DTL.ConclusionsWe conclude that the combination of real-life inhalation profiles with respective mouth-throat models and in vitro determination of delivered DTL is a good predictor of the drug delivery to children via the Respimat with VHC. The data provided can be used to support data from appropriate clinical trials.
| S-EPMC4739345 | biostudies-literature
Project description:ObjectiveTo introduce a novel technology currently under final development before regulatory approvals for the furtherment of cataract surgery, using the FemtoMatrix® laser system, and to demonstrate its safety and efficacy as compared to standard ultrasound phacoemulsification.MethodsThirty-three patients with bilateral cataracts were operated on with one eye undergoing PhotoEmulsification® treatment on the FemtoMatrix® device and the contralateral eye receiving the control procedure, i.e., standard ultrasound phacoemulsification treatment. The number of "zero-phaco" procedures (denoting that I/A alone was sufficient to aspirate the lens fragments and that no ultrasound energy was needed) was recorded and Effective Phaco Time (EPT) values were compared. The patient follow-up was 3 months.ResultsThirty-three eyes from a population with a mean cataract grade of 2.6 were treated on the FemtoMatrix®, of which 29 were "zero-phaco" (88%). All patients were operated on by a single surgeon who was a relative novice to the technology (63 patients treated prior to this study). Conversely, of the 33 fellow eyes who underwent standard ultrasound phacoemulsification, none were zero-phaco (0%) - all required varying degrees of ultrasound energy to make lens aspiration possible. The mean EPT was significantly lower in the PhotoEmulsification® laser group (0.2 ± 0.8 s) than in the phaco group (1.3 ± 1.2 s) (p < 0.0001). The safety profiles of the two procedures were comparable, with no device-related adverse events noted.ConclusionFemtoMatrix® is a promising femtosecond laser platform that, when compared to phacoemulsification, significantly decreases or eliminates EPT altogether. The system is used to perform PhotoEmulsification®, making zero-phaco cataract procedures feasible including in high-grade cataracts (>3). It enables personalized treatment by automatically measuring and adapting the laser energy required to obtain the most efficient cutting of the crystalline lens. This new technology appears to be safe and effective in cataract surgery.
| S-EPMC10149859 | biostudies-literature
Project description:IntroductionThe CIMZIA® AutoClicks® pre-filled pen (CZP PFP) was developed to overcome barriers to self-injection, by improving self-injection confidence, reducing fear associated with needle use, and supporting patients with impaired dexterity. The purpose of this research was to gather feedback on injection experience and the usefulness of training materials.MethodsEligible patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) were at least 18 years of age and initiated onto the CZP PFP. Routine self-injection training and support were provided by trained specialist nurses. Patient experience (pain and skin reactions, confidence, satisfaction, and ease of use) was evaluated at visits 1-3 using an amended version of the self-injection assessment questionnaire (SIAQ) v2.0. Nurse and patient feedback on the training materials, and nurse opinions on patient self-injection after self-injection at visit 1, were also collected.ResultsOf 355 patients invited to participate, 196 provided informed consent and 79 participated in all three visits. Patients generally found the CZP PFP easy to use, and self-confidence and satisfaction were high. From visit 1 to visit 3, there was a numerical trend towards improvement in all three aspects of patient experience, most notably in both confidence and satisfaction. After self-injection at visit 1, confidence around safe patient self-injection was higher among nurses than among patients. Meanwhile, "pain and skin reactions" remained low at all visits. Patients thought the training materials contained sufficient information and were easy to understand and useful.ConclusionAfter training, patients generally found the device easy to use and showed high confidence and satisfaction with self-injection. Some patients may have been competent (based on nurse opinion), but initially lacked self-confidence. Increasing self-injection experience, together with patient training and continued support, may have facilitated high patient confidence and satisfaction, thereby potentially overcoming some of the barriers to self-injection.
| S-EPMC7140744 | biostudies-literature
Project description:Human natural killer (NK) cells in lymphoid tissues can be categorized into three subsets: CD56brightCD16+, CD56dimCD16+ and CD69+CXCR6+ lymphoid tissue-resident (lt)NK cells. How the three subsets are functionally and developmentally related is currently unknown. Therefore, we performed single-cell RNA sequencing combined with oligonucleotide-conjugated antibodies against CD56, CXCR6, CD117 and CD34 on fresh bone marrow NK cells. A minor CD56dimGzmK+ subset was identified that shared features with CD56bright and CD56dimGzmK- NK cells based on transcriptome, phenotype (NKG2AhighCD16lowKLRG1highTIGIThigh) and functional analysis in bone marrow and blood, supportive for an intermediate subset. Pseudotime analysis positioned CD56bright, CD56dimGzmK+ and CD56dimGzmK- cells in one differentiation trajectory, while ltNK cells were developmentally separated. Integrative analysis with bone marrow cells from the Human Cell Atlas did not demonstrate a developmental connection between CD34+ progenitor and NK cells, suggesting absence of early NK cell stages in bone marrow. In conclusion, single-cell transcriptomics provide new insights on development and differentiation of human NK cells.
| S-EPMC9730327 | biostudies-literature
Project description:Background: Mesioangular impacted mandibular third molar is a common dental anomaly, for which surgical extraction is required. Post-surgery closure of mucosa reduces the prevalence of pain and other surgery-associated complications. We compared tissue reaction/inflammation after 3 and 7 days of mucosal closure with Trusilk ® and Mersilk ® silk sutures, following impacted mandibular third molar removal. Methods: This multicenter, prospective, two-arm, parallel-group, randomized (1:1), single-blind study (July 2020-November 2021) included subjects (Trusilk ®, n=65 and Mersilk ®, n=64), requiring mucosal suturing following impacted mandibular third molar removal. The primary endpoint, incidence of pain, swelling and trismus at the extraction area on post-surgery day 3 and 7 was evaluated. The secondary endpoints, incidence of tissue reaction, wound infection, suture loosening, other complications, operative time, amount of anesthesia, intraoperative suture handling, time needed for complete wound healing and suture removal, and adverse events were also recorded. Results: Socio-demographic and intra-oral characteristics were comparable between the groups. In Trusilk ® and Mersilk ® groups, a gradually decreasing pain score, starting from day 0 post-surgery (42.17±22.38 vs. 45.97±22.20) to day 7 (8.40±11.93 vs. 8.28±12.13) to day 30 (1.98±0.89 vs. 1.75±0.76) was witnessed. After the surgery, 21.54% and 17.19% subjects in Trusilk ® and Mersilk ® groups, respectively, had no post-operative swelling, while at the last two visits none of the subjects had swelling. Non-significant difference in wound infection, suture loosening, wound healing, bleeding, taste changes, operative time, amount of anesthesia, intraoperative suture handling, and time needed for complete wound healing and suture removal was noted among the groups. No suture-related adverse events were recorded. Conclusions: The results indicated that the Trusilk ® and Mersilk ® silk sutures are clinically equivalent and can be used for mucosal closure after removal of an impacted mandibular third molar with a minimal rate of pain, swelling and trismus. Clinical Trial Registry of India Registration: CTRI/2020/03/024100 (20/03/2020).
| S-EPMC9468627 | biostudies-literature
Project description:Neurological-related disorders are seen as an increasingly important aspect of welfare. While conventional medicine is still the mainstay for the treatment of these diseases, it is becoming apparent that patients are also seeking more natural and preventative interventions. Panax ginseng G115® and Ginkgo biloba GK501® extracts alone or in combination were used in two in vitro experimental models of primary cultures exposed to excitotoxicity: rat organotypic hippocampal slices exposed to either 5 µM kainic acid or 10 µM N-Methyl-d-aspartate for 24 hours, and mixed cortical cells exposed to 300 µM NMDA for 10 min. Cell death in the Cornu Ammonis areas CA3 or CA1 subregions of slices was quantified by measuring propidium iodide fluorescence, whereas in cortical cells, it was assessed by measuring the amount of lactate dehydrogenase. In slices, treatment with extracts alone or in combination significantly attenuated CA3 and CA1 damage induced by exposure to kainic acid or NMDA, respectively. A similar neuroprotective effect was observed in cortical cells exposed to NMDA. Analysis of cell signaling pathways found that the two extracts induced an increase of the phosphorylation and they reversed the decrease of phosphorylation of ERK1/2 and Akt induced by kainic acid and NMDA in organotypic hippocampal slices. These results suggest that P. ginseng G115® and G. biloba GK501® extracts may mediate their effects by activating phosphorylation of ERK1/2 and Akt signaling pathways, protecting against excitotoxicity-induced damage in in vitro models.
| S-EPMC6929202 | biostudies-literature
Project description:ObjectiveOmega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), likely prevent cardiovascular disease, however their mechanisms remain unclear. Recently, the role of DNA damage in atherogenesis has been receiving considerable attention. Here, we investigated the effects of EPA and DHA on DNA damage in vascular endothelial cells to clarify their antiatherogenic mechanisms.Methods and resultsWe determined the effect of EPA and DHA on H2O2-induced DNA damage response in human aortic endothelial cells. Immunofluorescence staining showed that γ-H2AX foci formation, a prominent marker of DNA damage, was significantly reduced in the cells treated with EPA and DHA (by 47% and 48%, respectively). H2O2-induced activation of ATM, a major kinase orchestrating DNA damage response, was significantly reduced with EPA and DHA treatment (by 31% and 33%, respectively). These results indicated EPA and DHA attenuated DNA damage independently of the DNA damage response. Thus the effects of EPA and DHA on a source of DNA damage were examined. EPA and DHA significantly reduced intracellular reactive oxygen species under both basal condition and H2O2 stimulation. In addition, the mRNA levels of antioxidant molecules, such as heme oxygenase-1, thioredoxin reductase 1, ferritin light chain, ferritin heavy chain and manganese superoxide dismutase, were significantly increased with EPA and DHA. Silencing nuclear factor erythroid 2-related factor 2 (NRF2) remarkably abrogated the increases in mRNA levels of antioxidant molecules and the decrease in intracellular reactive oxygen species. Furthermore, EPA and DHA significantly reduced H2O2-induced senescence-associated β-galactosidase activity in the cells (by 31% and 22%, respectively), which was revoked by NRF2 silencing.ConclusionsOur results suggested that EPA and DHA attenuate oxidative stress-induced DNA damage in vascular endothelial cells through upregulation of NRF2-mediated antioxidant response. Therefore omega-3 fatty acids likely help prevent cardiovascular disease, at least in part, by their genome protective properties.
| S-EPMC5679535 | biostudies-literature