Collagen-polyurethane-dextran hydrogels enhance wound healing by inhibiting inflammation and promoting collagen fibrillogenesis.

Diabetic foot ulcers are a serious complication of uncontrolled diabetes, emphasizing the need to develop wound healing strategies that are not only effective but also biocompatible, biodegradable, and safe. We aimed to create biomatrices composed of semi-interpenetrated polymer networks of collagen, polyurethane, and dextran, to enhance the wound healing process. The hydrogels were extensively characterized by various analytical techniques, including analysis of their structure, crystallinity, thermal properties, gelation process, reticulation, degradation, cell proliferation, and healing properties, among others. Semi-interpenetrated hydrogels containing dextran at levels of 10%, 20%, and 30% exhibited porous interconnections between collagen fibers and entrapped dextran granules, with a remarkable crosslinking index of up to 94% promoted by hydrogen bonds. These hydrogels showed significant improvements in mechanical properties, swelling, and resistance to proteolytic and hydrolytic degradation. After 24 h, there was a significant increase in the viability of several cell types, including RAW 264.7 cells, human peripheral blood mononuclear cells, and dermal fibroblasts. In addition, these hydrogels demonstrated an increased release of interleukin-10 and transforming growth factor-beta1 while inhibiting the release of monocyte chemotactic protein-1 and tumor necrosis factor-alpha after 72 h. Furthermore, these hydrogels accelerated the wound healing process in diabetic rats after topical application. Notably, the biomaterial with 20% dextran (D20) facilitated wound closure in only 21 days. These results highlight the potential of the D20 hydrogel, which exhibits physicochemical and biological properties that enhance wound healing by inhibiting inflammation and fibrillogenesis while remaining safe for application to the skin.

Determination of Nutritional and Antioxidant Properties of Maya Nut Flour (Brosimum alicastrum) for Development of Functional Foods.

Maya nut (Brosimum alicastrum) is a novel food with high nutritional value. This research aimed to evaluate the nutritional and antioxidant properties of Maya nut flour (MNF) made from seeds dried by different methods (sun-dried and using hot air at 45 °C and 60 °C) to explore its incorporation into cookies and evaluate its nutritional and functional properties. The naturally sun-dried flour (NF) had the highest content of ash (3.64 ± 0.11 g/100 g), protein (6.35 ± 0.44 g/100 g), crude fiber (6.75 ± 0.29 g/100 g), and functional properties (water and oil absorption). The color of the flour was affected by the different drying methods. While the drying methods influenced the total polyphenolic content (TPC) and antioxidant activity (AA) of MNF, they did not affect the morphology of the native starch or generated important molecular-structural changes. The substitution of 60% of wheat flour with NF in the cookie's formula increased the protein and fiber content, whereas 20% substitution increased its AA. MNF is a source of protein, dietary fiber, micronutrients, and functional compounds that can enrich cookie formulations.

Smart hydrogels based on semi-interpenetrating polymeric networks of collagen-polyurethane-alginate for soft/hard tissue healing, drug delivery devices, and anticancer therapies.

In this work, hydrogels based on semi-interpenetrating polymeric networks (semi-IPN) based on collagen-polyurethane-alginate were studied physicochemically and from different approaches for biomedical application. It was determined that the matrices in the hydrogel state are crosslinked by the formation of urea and amide bonds between the biopolymer chains and the polyurethane crosslinker. The increment in alginate content (0-40 wt%) significantly increases the swelling capacity, generating semi-crystalline granular structures with improved storage modulus and resistance to thermal, hydrolytic, and proteolytic degradation. The in vitro bioactivity results indicated that the composition of these novel hydrogels stimulates the metabolic activity of monocytes and fibroblasts, benefiting their proliferation; while in cancer cell lines, it was determined that the composition of these biomaterials decreases the metabolic activity of breast cancer cells after 48 h of stimulation, and for colon cancer cells their metabolic activity decreases after 72 h of contact for the hydrogel with 40 wt% alginate. The matrices show a behavior of multidose release of ketorolac, and a higher concentration of analgesic is released in the semi-IPN matrix. The inhibition capacity of Escherichia coli is higher if the polysaccharide concentration is low (10 wt%). The in vitro wound closure test (scratch test) results indicate that the hydrogel with 20 wt% alginate shows an improvement in wound closure at 15 days of contact. Finally, the bioactivity of mineralization was evaluated to demonstrate that these hydrogels can induce the formation of carbonated apatite on their surface. The engineered hydrogels show biomedical multifunctionality and they could be applied in soft and hard tissue healing strategies, anticancer therapies, and drug release devices.

Phase 1 First-in-Human Dose Escalation and Dose Expansion Study of KLS-1 (64Zinc Aspartate) in Patients With Cancer and Neurodegenerative Diseases.

Background KLS-1 is zinc (Zn) aspartate enriched with isotope 64Zn to 99.2% mass fraction of total zinc. KLS-1 is intended as a novel therapeutic approach for patients with a variety of diseases including but not limited to different forms of cancer and neurodegenerative diseases. The purpose of this first-in-human study was to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics (PK) in patients with medical disorders. Methods The study was designed as consisting of two consecutive parts: the dose escalation part and the dose expansion part. Adult patients with refractory glioblastoma, primary progressive aphasia/dementia, amyotrophic lateral sclerosis, Parkinson's disease (PD), and type 1 diabetes were included. KLS-1 formulated as a 10 mL water solution containing 26.42 mg/mL of 64zinc aspartate (that is equivalent to 5.184 mg/mL of 64Zn) was administered twice weekly in two-week cycles via two-hour intravenous (IV) infusion at various dose levels during the dose escalation part and twice weekly during five subsequent weeks in the dose expansion part. The study was conducted at Pan American Cancer Treatment Center (Tijuana, Mexico) in 2020 and had a duration of 10 months. Results A total of eight patients (all white/Caucasian) were enrolled in both parts of the study. A total of four patients who participated in the dose escalation part were dosed twice weekly at 1, 2, and 4 mg/kg in two-week cycles for each dose level with the dose increased to the next higher level in the subsequent cycle. Dose-limiting toxicities (DLTs) were defined at dose level 4 mg/kg due to treatment-emergent reversible adverse events that required medications for symptomatic relief. The most common drug-related toxicities that occurred in two or more patients (≥25%) were weakness (five patients), fatigue (four patients), dizziness (three patients), nausea (two patients), poor sleep (two patients), and abdominal discomfort (two patients). In the dose expansion part, a dose of 2 mg/kg administered twice weekly was investigated for five continuous weeks in four patients and was established as recommended phase 1b/2 dose. Systemic exposure to KLS-1 (area under the curve (AUC) and maximum serum concentration (Cmax)) increased from 1 to 4 mg/kg and showed a linear relationship. Conclusions Multiple doses of KLS-1 ranging from 1 to 2 mg/kg administered twice a week via intravenous infusion for up to five continuous weeks were safe and well tolerated in patients with different types of therapeutic conditions including but not limited to a few forms of cancer and Parkinson's disease, and the evaluated pharmacokinetic parameters exhibited favorable profile.

Correction: Phase 1 First-in-Human Dose Escalation and Dose Expansion Study of KLS-1 (64Zinc Aspartate) in Patients With Cancer and Neurodegenerative Diseases.

[This corrects the article DOI: 10.7759/cureus.29921.].

Hydroxyapatite and Biopolymer Composites with Promising Biomedical Applications

ABSTRACT The purpose of tissue engineering (regenerative medicine) is to develop materials that replace human tissue, having as main characteristics' biodegradability, biocompatibility, no toxicity, osteoconductivity, which lead to cell maturation and proliferation. Due to the importance of the development of this type of materials, several researchers have used biopolymers and calcium phosphate salts (hydroxyapatite) as composites to be used in this area as drug releases, scaffolds, implants, among others. Different biopolymers can be suitable for this type of application, in this work we have described the most widely used biopolymers for biomedical purposes, such as alginate, collagen, gellan gum, chitosan, and polylactic acid, in addition to a detailed description of hydroxyapatite, biopolymers, as well as biopolymer/hydroxyapatite composites, to highlight their potential and the most relevant characteristics of these materials.

Fungal Proteins from Sargassum spp. Using Solid-State Fermentation as a Green Bioprocess Strategy.

The development of green technologies and bioprocesses such as solid-state fermentation (SSF) is important for the processing of macroalgae biomass and to reduce the negative effect of Sargassum spp. on marine ecosystems, as well as the production of compounds with high added value such as fungal proteins. In the present study, Sargassum spp. biomass was subjected to hydrothermal pretreatments at different operating temperatures (150, 170, and 190 °C) and pressures (3.75, 6.91, and 11.54 bar) for 50 min, obtaining a glucan-rich substrate (17.99, 23.86, and 25.38 g/100 g d.w., respectively). The results indicate that Sargassum pretreated at a pretreatment temperature of 170 °C was suitable for fungal growth. SSF was performed in packed-bed bioreactors, obtaining the highest protein content at 96 h (6.6%) and the lowest content at 72 h (4.6%). In contrast, it was observed that the production of fungal proteins is related to the concentration of sugars. Furthermore, fermentation results in a reduction in antinutritional elements, such as heavy metals (As, Cd, Pb, Hg, and Sn), and there is a decrease in ash content during fermentation kinetics. Finally, this work shows that Aspergillus oryzae can assimilate nutrients found in the pretreated Sargassum spp. to produce fungal proteins as a strategy for the food industry.

Insecticidal capacity of polyphenolic seed compounds from neem (Azadirachta indica) on Spodoptera frugiperda (J. E. Smith) larvae.

The objective of this study was to evaluate the insecticidal activity of the polyphenolic compounds found in neem on S. frugiperda larvae. Three neem extracts (1:12 (m/v) with 70% ethanol, 1:12 (m/v) with 0% ethanol (only water), and 1:4 (m/v) with 0% ethanol) were employed. Subsequently, the extraction of phytochemical compounds of each extract was performed using ultrasound and microwave technologies simultaneously. The compound characterization was performed by HPLC-mass. In addition, the insecticidal evaluation of the neem extract was performed against S. frugiperda of the second-stage larvae. The extracts were applied by spraying the larvae according to each bioassay. Results showed that the extract obtained with a 1:12 (m/v) relationship and 70% ethanol was effective for the control of S. frugiperda larvae. In this extract, the predominant organic compound families were: methoxyflavones, flavonols, hydroxycoumarins, anthocyanins, methoxycinnamic acid, and alkylflavones. Phytochemical compounds obtained from neem seeds with environmentally friendly solvents and alternative technologies (ultrasound and microwave) have potent insecticidal activity against S. frugiperda larvae.

Green Bean, Pea and Mesquite Whole Pod Flours Nutritional and Functional Properties and Their Effect on Sourdough Bread.

In this study, proximal composition, mineral analysis, polyphenolic compounds identification, and antioxidant and functional activities were determined in green bean (GBF), mesquite (MF), and pea (PF) flours. Different mixtures of legume flour and wheat flour for bread elaboration were determined by a simplex-centroid design. After that, the proximal composition, color, specific volume, polyphenol content, antioxidant activities, and functional properties of the different breads were evaluated. While GBF and PF have a higher protein content (41-47%), MF has a significant fiber content (19.9%) as well as a higher polyphenol content (474.77 mg GAE/g) and antioxidant capacities. It was possible to identify Ca, K, and Mg and caffeic and enolic acids in the flours. The legume-wheat mixtures affected the fiber, protein content, and the physical properties of bread. Bread with MF contained more fiber; meanwhile, PF and GBF benefit the protein content. With MF, the specific bread volume only decreased by 7%. These legume flours have the potential to increase the nutritional value of bakery goods.

Phytochemical Characterization of Phoradendron bollanum and Viscum album subs. austriacum as Mexican Mistletoe Plants with Antimicrobial Activity.

In Mexico, mistletoes have several applications in traditional medicine due to the great variety of compounds with biological activities that have not been characterized to date. The goals of the present study are to analyze the composition of minerals and phytochemical compounds in Mexican mistletoes Phoradendron bollanum and Viscum album subs. austriacum qualitatively and quantitatively, identify the compounds using HPLC-MS, and assess the antimicrobial potential in phytopathogenic microorganism control. Mineral content was evaluated with X-ray fluorescence. Three types of extracts were prepared: ethanol, water, and aqueous 150 mM sodium chloride solution. Characterization was carried out using qualitative tests for phytochemical compound groups, analytical methods for proteins, reducing sugars, total phenol, flavonoids quantification, and HPLC-MS for compound identification. The antimicrobial activity of mistletoe's liquid extracts was evaluated by microplate assay. K and Ca minerals were observed in both mistletoes. A qualitative test demonstrated alkaloids, carbohydrates, saponins, flavonoids, tannins, and quinones. Ethanolic extract showed flavonoids, 3845 ± 69 and 3067 ± 17.2 mg QE/g for Phoradendron bollanum and Viscum album subs. austriacum, respectively, while aqueous extracts showed a total phenol content of 65 ± 6.9 and 90 ± 1.19 mg GAE/g Phoradendron bollanum and Viscum album subs. austriacum, respectively. HPLC-MS identified largely hydroxycinnamic acids and methoxycinnamic acids. Clavibacter michiganenses was successfully inhibited by aqueous extract of both mistletoes.

Goethite-titania composite: disinfection mechanism under UV and visible light.

Goethite-titania (α-FeOOH-TiO2) composites were prepared by co-precipitation and mechanical milling. The structural, morphological and optical properties of as-synthesized composites were characterized by X-ray powder diffraction, scanning electron microscopy and UV-Vis diffuse reflectance spectroscopy, respectively. α-FeOOH-TiO2 composites and TiO2-P25, as reference, were evaluated as photocatalysts for the disinfection of Escherichia coli under UV or visible light in a stirred tank reactor. α-FeOOH-TiO2 exhibited better photocatalytic activity in the visible region than TiO2-P25. The mechanical activation increased the absorption in the visible range of TiO2-P25 and the photocatalytic activity of α-FeOOH-TiO2. In the experiments with UV light and α-FeOOH-TiO2, mechanically activated, a 5.4 log-reduction of bacteria was achieved after 240 min of treatment. Using visible light the α-FeOOH-TiO2 and the TiO2-P25 showed a 3.1 and a 0.7 log-reductions at 240 min, respectively. The disinfection mechanism was studied by ROS detection and scavenger experiments, demonstrating that the main ROS produced in the disinfection process were superoxide radical anion, singlet oxygen and hydroxyl radical.

Role of caspases in cytokine-induced barrier breakdown in human brain endothelial cells.

During neuroinflammation, cytokines such as TNF-α and IFN-γ secreted by activated leukocytes and/or CNS resident cells have been shown to alter the phenotype and function of brain endothelial cells (BECs) leading to blood-brain barrier breakdown. In this study, we show that the human BEC line hCMEC/D3 expresses the receptors for TNF-α, TNF receptor 1 and TNF receptor 2, and for IFN-γ. BEC activation with TNF-α alone or in combination with IFN-γ induced endothelial leakage of paracellular tracers. At high cytokine concentrations (10 and 100 ng/ml), this effect was associated with caspase-3/7 activation and apoptotic cell death as evidenced by annexin V staining and DNA fragmentation (TUNEL) assays. In addition, inhibition of JNK and protein kinase C activation at these doses partially prevented activation of caspase-3/7, although only JNK inhibition was partially able to prevent the increase in BEC paracellular permeability induced by cytokines. By contrast, lower cytokine concentrations (1 ng/ml) also led to effector caspase activation, increased paracellular flux, and redistribution of zonula occludens-1 and VE-cadherin but failed to induce apoptosis. Under these conditions, specific caspase-3 and caspase-9, but not caspase-8, inhibitors partially blocked cytokine-induced disruption of tight and adherens junctions and BEC paracellular permeability. Our results suggest that the concentration of cytokines in the CNS endothelial microenvironment determines the extent of caspase-mediated barrier permeability changes, which may be generalized as a result of apoptosis or more subtle as a result of alterations in the organization of junctional complex molecules.

Acompañamiento familiar en la hospitalización del usuario pediátrico de 6 a 12 años / Family support during hospitalization of the 6 to 12 years old pediatric user

Antecedentes. La hospitalización genera en el niño una adaptación al nuevo entorno, situación que produce estrés producto del cambio de ambiente, en donde la separación de sus padres de su entorno típico es un tema interesante de abordar para comprender el perfil del acompañante. Objetivo. Describir los tipos de acompañamiento familiar más frecuentes durante la hospitalización del usuario pediátrico de 6 a 12 años en el Centro de Costo Indiferenciado del Niño y la Niña (CCINN), del Complejo Asistencial Dr. Víctor Ríos Ruiz de la ciudad de Los Ángeles, Chile. Material y método. Estudio descriptivo de corte transversal, en el cual se seleccionó a 52 usuarios pediátricos entre 6 a 12 años hospitalizados en el CCINN del Complejo Asistencial Dr. Víctor Ríos Ruiz de Los Ángeles. Resultados. El 92,3 por ciento de los padres y/o cuidadores que visitan a sus hijos están interesados en entender la situación actual del niño/a en su hospitalización y enfermedad (acompañamiento familiar tipo 1), mientras que un 7,7 por ciento de la muestra de padres con un esfuerzo disminuido (acompañamiento familiar tipo 2) (z=4,10; p<0,001), no registrando padres y/o cuidadores con conductas de bajo o escaso interés por la situación actual del niño/a que pudiera dificultar su integración frente a la situación de hospitalización y enfermedad (acompañamiento familiar tipo 3). Conclusión. Se logra evidenciar una preocupación de los padres y/o cuidadores por el proceso que vive el hijo y/o pupilo, en donde los profesionales pueden integrarse mediante la educación de técnicas o materias del cuidado posthospitalización del usuario pediátrico.

Background. The hospital generates in the child adaptation to a new environment, a situation that produces stress because of the change, where the separation of their parents from their typical environment is an interesting topic to address in order to understand the profile of the accompanying person. Objective. To describe the types of most frequent family company observed during the hospitalization of the 6 to 12 years old pediatric user in the Child Undifferentiated Cost Center (UCCCh). Methods. Cross-sectional descriptive study, which selected 52 pediatric users aged 6 to 12, hospitalized in UCCCh at Dr. Víctor Ríos Ruiz Hospital, Los Ángeles, Chile. Results. 92.3 percent of parents and / or caregivers who visit their children are interested in understand the current situation of the child in his/her hospitalization and illness (family support type 1), while 7.7 percent of the sample shows declined efforts of parents (family support type 2) (z=4.10, P<0.001), not registering parents / caregivers with a behavior that shows low or poor interest in the child’s current situation / that could impede their integration addressing the situation of hospitalization and illness (family support type 3). Conclusion. It does demonstrate a concern from parents/caregivers through the process experienced by the child, where professionals can integrate them through education techniques or some care contents post-hospitalization for pediatric user.

Tindallia texcoconensis sp. nov., a new haloalkaliphilic bacterium isolated from lake Texcoco, Mexico.

A new alkaliphilic and moderately halophilic, strictly anaerobic, fermentative bacterium (strain IMP-300(T)) was isolated from a groundwater sample in the zone of the former soda lake Texcoco in Mexico. Strain IMP-300(T) was Gram-positive, non-sporulated, motile and rod-shaped. It grew within a pH range from 7.5 to 10.5, and an optimum at 9.5. The organism was obligately dependent on the presence of sodium salts. Growth showed an optimum at 35 degrees C with absence of growth above 45 degrees C. It fermented peptone and a few amino acids, preferentially arginine and ornithine, with production of acetate, propionate, and ammonium. Its fatty acid pattern was mainly composed of straight chain saturated, unsaturated, and cyclopropane fatty acids. The G + C content of genomic DNA was 40.0 mol%. Analysis of the 16S rRNA gene sequence indicated that the new isolate belongs to the genus Tindallia, in the low G + C Gram-positive phylum. Phylogenetically, strain IMP-300(T) has Tindallia californiensis, as closest relative with a 97.5% similarity level between their 16S rDNA gene sequences, but the DNA-DNA re-association value between the two DNAs was only 42.2%. On the basis of differences in genotypic, phenotypic, and phylogenetic characteristics, strain IMP-300(T) is proposed as a new species of the genus Tindallia, T. texcoconensis sp. nov. (type strain IMP-300(T ) = DSM 18041(T) = JCM 13990(T)).