In embryogenesis, coronary blood vessels are formed by vasculogenesis from epicardium-derived progenitors. Subsequently, growing or regenerating myocardium increases its vasculature by angiogenesis, ...forming new vessels from the pre-existing ones. Recently, cell therapies for myocardium ischemia that used different protocols have given promising results, using either extra-cardiac blood vessel cell progenitors or stimulating the cardiac angiogenesis. We have questioned whether cardiomyocytes could sustain both vasculogenesis and angiogenesis. We used a 3D culture model of tissue-like spheroids in co-cultures of cardiomyocytes supplemented either with endothelial cells or with bone marrow-derived mesenchymal stroma cells. Murine foetal cardiomyocytes introduced into non-adherent U-wells formed 3D contractile structures. They were coupled by gap junctions. Cardiomyocytes segregated inside the 3D structure into clumps separated by connective tissue septa, rich in fibronectin. Three vascular endothelial growth factor isoforms were produced (VEGF 120, 164 and 188). When co-cultured with human umbilical cord endothelial cells, vascular structures were produced in fibronectin-rich external layer and in radial septa, followed by angiogenic sprouting into the cardiomyocyte microtissue. Presence of vascular structures led to the maintenance of long-term survival and contractile capacity of cardiac microtissues. Conversely, bone marrow mesenchymal cells formed isolated cell aggregates, which progressively expressed the endothelial markers von Willebrand's antigen and CD31. They proceeded to typical vasculogenesis forming new blood vessels organised in radial pattern. Our results indicate that the in vitro 3D model of cardiomyocyte spheroids provides the two basic elements for formation of new blood vessels: fibronectin and VEGF. Within the myocardial environment, endothelial and mesenchymal cells can proceed to formation of new blood vessels either through angiogenesis or vasculogenesis, respectively.
► Polysaccharide from marine alga Gracilaria caudata (PGC) was recovery with 32.8% of yield. ► Characterization was performed by microanalysis, FT-IR and NMR spectroscopy. ► The structure is ...constituted by β-d-galactopyranose and 6-α-l-anhydrogalactose. ► Methyl and pyruvic acid groups were also detected.
Seaweeds are considered an important source of bioactive molecules. In this work the marine red alga Gracilaria caudata was submitted to aqueous extraction of their polysaccharides for 2h at 100°C. The polysaccharide fraction (PGC) presented a recovery of 32.8%. The sulfate content of PGC, calculated by S%, is 1±0.2% and the degree of sulfation accounts for 0.13±0.2. High-Performance Size-Exclusion Chromatography demonstrated that PGC consists of a high molecular weight polysaccharide (2.5×105gmol−1). Chemical analysis of PGC was performed by microanalysis, infrared (FT-IR) and nuclear magnetic resonance (NMR, 1 and 2D) spectroscopy. The structure of PGC is mainly constituted by the alternating residues 3-linked-β-d-galactopyranose and 4-linked-3,6-α-l-anhydrogalactose; however some hydroxyl groups were substituted by methyl groups and pyruvic acid acetal. The biological precursor of 3,6-α-l-anhydrogalactose (6-sulfate-α-l-galactose) was also detected.
Objectives. To evaluate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over 6 months in the Brazilian State of Rio Grande do Sul (population 11.3 million), based on 8 ...serological surveys.
Methods. In each survey, 4151 participants in round 1 and 4460 participants in round 2 were randomly sampled from all state regions. We assessed presence of antibodies against SARS-CoV-2 using a validated lateral flow point-of-care test; we adjusted figures for the time-dependent decay of antibodies.
Results. The SARS-CoV-2 antibody prevalence increased from 0.03% (95% confidence interval CI = 0.00%, 0.34%; 1 in every 3333 individuals) in mid-April to 1.89% (95% CI = 1.36%, 2.54%; 1 in every 53 individuals) in early September. Prevalence was similar across gender and skin color categories. Older adults were less likely to be infected than younger participants. The proportion of the population who reported leaving home daily increased from 21.4% (95% CI = 20.2%, 22.7%) to 33.2% (95% CI = 31.8%, 34.5%).
Conclusions. SARS-CoV-2 infection increased slowly during the first 6 months in the state, differently from what was observed in other Brazilian regions. Future survey rounds will continue to document the spread of the pandemic.
•Sulfated polysaccharide (SFP) possess a high sulfate content.•The main constituent of the SFP is iota-carrageenan.•SFP reduced the oxidative stress and the gastric damage in vivo.•SFP also revealed ...the relevant antioxidant activity in vitro.
A sulfated polysaccharide (SFP) fraction from the marine alga Solieria filiformis was extracted and submitted to microanalysis, molar mass estimation and spectroscopic analysis. We evaluated its gastroprotective potential in vivo in an ethanol-induced gastric damage model and its in vitro antioxidant properties (DPPH, chelating ferrous ability and total antioxidant capacity). Its chemical composition revealed to be essentially an iota-carrageenan with a molar mass of 210.9kDa and high degree of substitution for sulfate groups (1.08). In vivo, SFP significantly (P<0.05) reduced, in a dose dependent manner, the ethanol-induced gastric damage. SFP prevents glutathione consume and increase of malondialdehyde and hemoglobin levels. SFP presented an IC50 of 1.77mg/mL in scavenging DPPH. The chelating ferrous ability was 38.98%, and the total antioxidant capacity was 2.01mg/mL. Thus, SFP prevents the development of ethanol-induced gastric damage by reducing oxidative stress in vivo and possesses relevant antioxidant activity in vitro.
► Polysaccharide fraction from P. edulcis flour (PFCM) was extracted with hot water. ► PFCM has homogalacturonan (HG) and rhamnogalacturonan-1 (RG-1) structures. ► The proportion of RG-1 structure is ...higher than HG structure. ► PFCM exhibited in vivo antitumor effects with no expressive toxicity.
A hot water-extracted polysaccharide fraction (PFCM) of Passiflora edulis was characterized by microanalysis, infrared spectroscopy, NMR and high performance size-exclusion chromatography. The major component in PFCM is (1→4) linked galacturonic acid (esterified and unesterified). Neutral sugars such as arabinose, glucose, rhamnose, mannose, and fucose were also present. Traces of xylose and ribose were detected. The PFCM sample had a similar molar mass to that of pectin extracted from P. edulis under acidic conditions. Sarcoma 180 tumors treated with PFCM showed a growth inhibition ratio ranging from 40.59% to 48.73% depending on the dosage and type of PFCM administration (oral or intraperitoneal). Toxicological analysis shows that PFCM increases the cell types involved in primary defense mechanisms and no significant changes in the biochemical parameters and organs (e.g., kidney and liver) were observed. However, the use of PFCM treatment increased the spleen weight when compared with the use of 5-fluorouracil.
Psoralens are widely used for the treatment of psoriasis. Trioxsalen is a drug prescribed low-dose, belonging to the group of substituted psoralen. The aim of this study was to evaluate the ...compatibility of trioxsalen with pharmaceutical excipients used in the solid forms by analytical techniques. Binary mixtures between the trioxsalen and pharmaceutical excipients (namely, magnesium stearate, α-lactose, microcrystalline cellulose 102, pregelatinized starch, mannitol, sodium lauryl sulfate, sodium starch glycolate, and croscarmellose sodium) were examined. The trioxsalen–sodium lauryl sulfate mixture displayed some physical interaction based on the DTA and DSC results, but the FTIR study ruled out any chemical change.
Background
Self-emulsifying drug delivery systems (SEDDSs) have attracted attention because of their effects on solubility and bioavailability of lipophilic compounds. Herein, a SEDDS loaded with ...lycopene purified from red guava (nanoLPG) was produced. The nanoemulsion was characterized using dynamic light scattering (DLS), zeta potential measurement, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), lycopene content quantification, radical scavenging activity and colloidal stability in cell culture medium. Then, in vivo toxicity and tissue distribution in orally treated mice and cytotoxicity on human prostate carcinoma cells (DU-145) and human peripheral blood mononuclear cells (PBMC) were evaluated.
Results
NanoLPG exhibited physicochemical properties with a size around 200 nm, negative zeta-potential, and spherical morphology. The size, polydispersity index, and zeta potential parameters suffered insignificant alterations during the 12 month storage at 5 °C, which were associated with lycopene stability at 5 °C for 10 months. The nanoemulsion showed partial aggregation in cell culture medium at 37 °C after 24 h. NanoLPG at 0.10 mg/mL exhibited radical scavenging activity equivalent to 0.043 ± 0.002 mg Trolox/mL. The in vivo studies did not reveal any significant changes in clinical, behavioral, hematological, biochemical, and histopathological parameters in mice orally treated with nanoLPG at 10 mg/kg for 28 days. In addition, nanoLPG successfully delivered lycopene to the liver, kidney and prostate in mice, improved its cytotoxicity against DU-145 prostate cancer cells—probably by pathway independent on classical necrosis and apoptosis—and did not affect PBMC viability.
Conclusions
Thus, nanoLPG stands as a promising and biosafe lycopene delivery system for further development of nanotechnology-based health products.
Graphical Abstract
Seaweeds are sources of diverse bioactive compounds, such as sulphated polysaccharides. This study was designed to evaluate the chemical composition and anti-diarrheal activity of a fraction of ...sulphated polysaccharide (PLS) obtained from the red seaweed Hypnea musciformis in different animal models, and to elucidate the underlying mechanisms. PLS was obtained by aqueous extraction, with a yield of 31.8% of the seaweed dry weight. The total carbohydrate content accounted for 99% of the sample. The sulfate content of the polysaccharide was 5.08% and the percentage of carbon was 25.98%. Pretreatment with all doses of PLS inhibited castor oil-induced diarrhea, with reduction of the total amount of stool, diarrheal stools, and the severity of diarrhea. PLS (90mg/Kg) decreased castor oil- and PGE2-induced enteropooling. In addition, PLS (90mg/Kg) increased the Na+/K+-ATPase activity in the small intestine and reduced gastrointestinal transit, possibly via activation of cholinergic receptors. Interestingly, the cholera toxin-induced fluid secretion and Cl− ion levels decreased in the intestinal contents of the animals pretreated with PLS (90mg/kg), probably via reduction of toxin—GM1 receptor binding. In conclusion, PLS exerts anti-diarrheal activity by increasing Na+/K+-ATPase activity, inhibiting gastrointestinal motility, and blocking the toxin—GM1 receptor binding.
Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of ...collagen and immunostaining for Transforming Growth Factor beta (TGF-β) in the clinical and microscopic findings of PG and POF.
PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-β) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0).
The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-β+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-β suffered from modifications by the time of evolution and the size of the lesion.
Although PG and POF are reactive gingival lesions, the expression of TGF-β and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.
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