Scaffolds for cultured meat on the basis of polysaccharide hydrogels enriched with plant-based proteins

The world population is growing and alternative ways of satisfying the increasing demand for meat are being explored, such as using animal cells for the fabrication of cultured meat. Edible biomaterials are required as supporting structures. Hence, we chose agarose, gellan and a xanthan-locust bean gum blend (XLB) as support materials with pea and soy protein additives and analyzed them regarding material properties and biocompatibility. We successfully built stable hydrogels containing up to 1% pea or soy protein. Higher amounts of protein resulted in poor handling properties and unstable gels. The gelation temperature range for agarose and gellan blends is between 23–30 °C, but for XLB blends it is above 55 °C. A change in viscosity and a decrease in the swelling behavior was observed in the polysaccharide-protein gels compared to the pure polysaccharide gels. None of the leachates of the investigated materials had cytotoxic effects on the myoblast cell line C2C12. All polysaccharide-protein blends evaluated turned out as potential candidates for cultured meat. For cell-laden gels, the gellan blends were the most suitable in terms of processing and uniform distribution of cells, followed by agarose blends, whereas no stable cell-laden gels could be formed with XLB blends

Scaffolds for Cultured Meat on the Basis of Polysaccharide Hydrogels Enriched with Plant-Based Proteins

The world population is growing and alternative ways of satisfying the increasing demand for meat are being explored, such as using animal cells for the fabrication of cultured meat. Edible biomaterials are required as supporting structures. Hence, we chose agarose, gellan and a xanthan-locust bean gum blend (XLB) as support materials with pea and soy protein additives and analyzed them regarding material properties and biocompatibility. We successfully built stable hydrogels containing up to 1% pea or soy protein. Higher amounts of protein resulted in poor handling properties and unstable gels. The gelation temperature range for agarose and gellan blends is between 23–30 °C, but for XLB blends it is above 55 °C. A change in viscosity and a decrease in the swelling behavior was observed in the polysaccharide-protein gels compared to the pure polysaccharide gels. None of the leachates of the investigated materials had cytotoxic effects on the myoblast cell line C2C12. All polysaccharide-protein blends evaluated turned out as potential candidates for cultured meat. For cell-laden gels, the gellan blends were the most suitable in terms of processing and uniform distribution of cells, followed by agarose blends, whereas no stable cell-laden gels could be formed with XLB blends

Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model

Abstract Background In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics. We aimed to investigate the prospect for success of a clinical ON trial using an experimental autoimmune encephalomyelitis-optic neuritis (EAE-ON) model with visual system readouts adaptable to a clinical ON trial. Methods Using an in vitro cell culture model for endogenous oxidative stress, we compared the neuroprotective capacity of racemic LA with the R/S-enantiomers and its reduced form. In vivo, we analyzed retinal neurodegeneration using optical coherence tomography (OCT) and the visual function by optokinetic response (OKR) in MOG35–55-induced EAE-ON in C57BL/6J mice. Ganglion cell counts, inflammation, and demyelination were assessed by immunohistological staining of retinae and optic nerves. Results All forms of LA provided equal neuroprotective capacities in vitro. In EAE-ON, prophylactic LA therapy attenuated the clinical EAE score and prevented the thinning of the inner retinal layer while therapeutic treatment was not protective on visual outcomes. Conclusions A prophylactic LA treatment is necessary to protect from visual loss and retinal thinning in EAE-ON, suggesting that a clinical ON trial starting therapy after the onset of symptoms may not be successful

Spontaneous Non-Sustained Ventricular Tachycardia and Premature Ventricular Contractions and Their Prognostic Relevance in Patients with Cancer in Routine Care

Aims: It is largely unknown whether cancer patients seen in routine care show ventricular arrhythmias in 24 h electrocardiograms (ECGs), and whether when they are detected they carry prognostic relevance. Methods and Results: We included 261 consecutive cancer patients that were referred to the department of cardiology for 24 h ECG examination and 35 healthy controls of similar age and sex in the analysis. To reduce selection bias, cancer patients with known left ventricular ejection fraction = 3 and >= 4 beats duration were more frequent in cancer patients than controls (17% vs. 0%, p = 0.0008; 10% vs. 0%, p = 0.016). Premature ventricular contractions (PVCs)/24 h were not more frequent in cancer patients compared to controls (median (IQR), 26 (2-360) vs. 9 (1-43), p = 0.06; >= 20 PVCs 53% vs. 37%, p = 0.07). During follow-up, (up to 7.2 years, median 15 months) of the cancer patients, 158 (61%) died (1-/3-/5-year mortality rates: 45% [95%CI 39-51%], 66% [95%CI 59-73%], 73% [95%CI 64-82%]). Both non-sustained ventricular tachycardia of >= 4 beats and >= 20 PVCs/24 h independently predicted mortality in univariate and multivariate survival analyses, adjusted for all other univariate predictors of mortality as well as relevant clinical factors, including cancer stage and type, performance status (ECOG), prior potentially cardiotoxic anti-cancer drug therapy, coronary artery disease, potassium concentration, and haemoglobin (multivariate adjusted hazard ratios: NSVT >= 4 beats [HR 1.76, p = 0.022], >= 20 PVCs/24 h [HR 1.63, p < 0.0064]). Conclusions: NSVT >= 4 beats and >= 20 PVCs/day seen in routine 24 h ECGs of patients with cancer carry prognostic relevance

Spontaneous Non-Sustained Ventricular Tachycardia and Premature Ventricular Contractions and Their Prognostic Relevance in Patients with Cancer in Routine Care

Aims: It is largely unknown whether cancer patients seen in routine care show ventricular arrhythmias in 24 h electrocardiograms (ECGs), and whether when they are detected they carry prognostic relevance. Methods and Results: We included 261 consecutive cancer patients that were referred to the department of cardiology for 24 h ECG examination and 35 healthy controls of similar age and sex in the analysis. To reduce selection bias, cancer patients with known left ventricular ejection fraction <45% were not included in the analysis. Non–sustained ventricular tachycardia (NSVT) episodes of either ≥3 and ≥4 beats duration were more frequent in cancer patients than controls (17% vs. 0%, p = 0.0008; 10% vs. 0%, p = 0.016). Premature ventricular contractions (PVCs)/24 h were not more frequent in cancer patients compared to controls (median (IQR), 26 (2–360) vs. 9 (1–43), p = 0.06; ≥20 PVCs 53% vs. 37%, p = 0.07). During follow-up, (up to 7.2 years, median 15 months) of the cancer patients, 158 (61%) died (1-/3-/5-year mortality rates: 45% [95%CI 39–51%], 66% [95%CI 59–73%], 73% [95%CI 64–82%]). Both non-sustained ventricular tachycardia of ≥4 beats and ≥20 PVCs/24 h independently predicted mortality in univariate and multivariate survival analyses, adjusted for all other univariate predictors of mortality as well as relevant clinical factors, including cancer stage and type, performance status (ECOG), prior potentially cardiotoxic anti-cancer drug therapy, coronary artery disease, potassium concentration, and haemoglobin (multivariate adjusted hazard ratios: NSVT ≥4 beats [HR 1.76, p = 0.022], ≥20 PVCs/24 h [HR 1.63, p < 0.0064]). Conclusions: NSVT ≥4 beats and ≥20 PVCs/day seen in routine 24 h ECGs of patients with cancer carry prognostic relevance. View Full-Text Keywords: ventricular arrhythmia; non-sustained ventricular tachycardia; ventricular premature contractions; cancer; surviva

Additional file 2: of Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model

Figure S1. LA treatment days before glutamate induced oxidative stress did not result in improved HT22 protection compared to a 24 h pre-incubation. 5000 cells were seeded into 96-well plates and pre-incubated 9 days (a), 6 days (b) or 2 days (c) before glutamate addition either with vehicle or 25 μM LA DHLA, (R)-LA or (S)-LA. Graphs represent curve fits ±SEM of four independent experiments, each performed in triplicates. Significant differences between vehicle- and substance-treatment are indicated by asterisks (***p < 0.001, area under the curve compared by ANOVA with Dunnett’s post hoc test). (PDF 256 kb

Additional file 4: of Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model

Figure S3. Optic nerves of sham-EAE, MOG-EAE and MOG-EAE with therapeutic LA treated mice were compared for microglia activation by fluorescence intensity measurement (a), by a CD3 score for T-cell Infiltration (b) and by a MBP myelination score for myelin status (c); quantitative analyses of the results of three independent EAE experiments with at least four mice are shown as bar graphs; one ON per mouse was included. (***p < 0.001, n.s. = not significant, by ANOVA with Dunnett’s post hoc test compared to MOG untreated mice). (PDF 227 kb

Additional file 1: of Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model

Table S1. Advised Protocol for OCT Study Terminology and Elements (APOSTEL) checklist; each item discussed in the manuscript on the indicated page. (PDF 30 kb

Additional file 3: of Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model

Figure S2. The carbonylation of proteins did not change 120 days after EAE immunization. The bar graphs represent the pooled mean ± standard deviation of at least three separate EAE experiments each with at least three animals per group (n.s. = not significant, by ANOVA with Dunnett’s post hoc test compared to MOG untreated mice). (PDF 165 kb