Hydrogels dressings based on guar gum and chitosan: Inherent action against resistant bacteria and fast wound closure.

Hydrogels made with depolymerized guar gum, oxidized with theoretical oxidation degrees of 20, 35 and 50 %, were obtained via Schiff's base reaction with N-succinyl chitosan. The materials obtained were subjected to characterization by FT-IR, rheology, swelling, degradation, and morphology. Additionally, their gelation time categorized all three hydrogels as injectable. The materials' swelling degrees in Phosphate-Buffered Saline (PBS) were in the range of 26-35 g of fluid/g gel and their pore size distribution was heterogeneous, with pores varying from 67 to 93 µm. All hydrogels degraded in PBS solution, but maintained around 40 % of their initial mass after 28 days, which was more than enough time for wound healing. The biomaterials were also flexible, self-repairing, adhesive and cytocompatible and presented intrinsic actions, regardless of the presence of additives or antibiotics, against gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli). However, the most pronounced bactericidal effect was against resistant Staphylococcus aureus - MRSA. In vivo assays, performed with 50 % oxidized gum gel, demonstrated that this material exerted anti-inflammatory effects, accelerating the healing process and restoring tissues by approximately 99 % within 14 days. In conclusion, these hydrogels have unique characteristics, making them excellent candidates for wound-healing dressings.

Development of a New Clay-Based Aerogel Composite from Ball Clay from Piauí, Brazil and Polysaccharides.

The incorporation of polymeric components into aerogels based on clay produces a significant improvement in the physical and thermal properties of the aerogels. In this study, clay-based aerogels were produced from a ball clay by incorporation of angico gum and sodium alginate using a simple, ecologically acceptable mixing method and freeze-drying. The compression test showed a low density of spongy material. In addition, both the compressive strength and the Young's modulus of elasticity of the aerogels showed a progression associated to the decrease in pH. The microstructural characteristics of the aerogels were investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The chemical structure was studied by infrared spectroscopy with Fourier transform (FTIR). The TGA curves from a non-oxidizing atmosphere indicated that the clay had a mass loss of 9% above 500 °C and that due to the presence of polysaccharides, the aerogels presented a decomposition of 20% at temperatures above 260 °C. The DSC curves of the aerogels demonstrated a displacement in higher temperatures. In conclusion, the results showed that aerogels of ball clay with the incorporation of polysaccharides, which are still minimally studied, have potential application as thermal insulation considering the mechanical and thermal results obtained.

Probing human proteins for short encrypted antimicrobial peptides reveals Hs10, a peptide with selective activity for gram-negative bacteria.

BACKGROUND: Some cationic and amphiphilic α-helical segments of proteins adsorb to prokaryotic membranes when synthesized as individual polypeptide sequences, resulting in broad and potent antimicrobial activity. However, amphiphilicity, a determinant physicochemical property for peptide-membrane interactions, can also be observed in some ß-sheets. METHODS: The software Kamal was used to scan the human reference proteome for short (7-11 amino acid residues) cationic and amphiphilic protein segments with the characteristic periodicity of ß-sheets. Some of the uncovered peptides were chemically synthesized, and antimicrobial assays were conducted. Biophysical techniques were used to probe the molecular interaction of one peptide with phospholipid vesicles, lipopolysaccharides (LPS) and the bacterium Escherichia coli. RESULTS: Thousands of compatible segments were found in human proteins, five were synthesized, and three presented antimicrobial activity in the micromolar range. Hs10, a nonapeptide fragment of the Complement C3 protein, could inhibit only the growth of tested Gram-negative microorganisms, presenting also little cytotoxicity to human fibroblasts. Hs10 interacted with LPS while transitioning from an unstructured segment to a ß-sheet and increased the hydrodynamic radius of LPS particles. This peptide also promoted morphological alterations in E. coli cells. CONCLUSIONS: Data presented herein introduce yet another molecular template to probe proteins in search for encrypted membrane-active segments and demonstrates that, using this approach, short peptides with low cytotoxicity and high selectivity to prokaryotic cells might be obtained. GENERAL SIGNIFICANCE: This work widens the biotechnological potential of the human proteome as a source of antimicrobial peptides with application in human health.

Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches.

Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets of SARS-CoV-2. 3D structures from DIZE and the proteases from SARS-CoV-2, obtained through the Protein Data Bank and Drug Database (Drubank), and processed in computer programs like AutodockTools, LigPlot, Pymol for molecular docking and visualization and GROMACS was used to perform molecular dynamics. The results demonstrate that DIZE could interact with all tested targets, and the best binding energies were obtained from the interaction of Protein S (closed conformation -7.87 kcal/mol) and Mpro (-6.23 kcal/mol), indicating that it can act both by preventing entry and viral replication. The results of molecular dynamics demonstrate that DIZE was able to promote a change in stability at the cleavage sites between S1 and S2, which could prevent binding to ACE2 and fusion with the membrane. In addition, in vitro tests confirm the in silico results showing that DIZE could inhibit the binding between the spike receptor-binding domain protein and ACE2, which could promote a reduction in the virus infection. However, tests in other experimental models with in vivo approaches are needed.

Rapid and selective detection of dopamine in human serum using an electrochemical sensor based on zinc oxide nanoparticles, nickel phthalocyanines, and carbon nanotubes.

Composite materials have gained significant attention owing to the synergistic effects of their constituent materials, thereby facilitating their utilization in new applications or in improving the existing ones. In this study, a composite based on nickel phthalocyanine (NiTsPc), zinc oxide nanoparticles (ZnONPs), and carbon nanotubes (CNT) was developed and subsequently immobilized on a pyrolytic graphite electrode (PGE). The PGE/NiTsPc-ZnONPs-CNT was identified as a selective catalytic hybrid system for detection of neurotransmitter dopamine (DA). The electrochemical and morphological characterizations were conducted using atomic force microscopy (AFM). Chronoamperometry and differential pulse voltammetry (DPV) were used to detect DA and detection limits of 24 nM and 7.0 nM was found, respectively. In addition, the effects of some possible DA interferents, such as ascorbic acid, uric acid, and serotonin, on DA response were evaluated. Their presence did not show significant variations in the DA electrochemical response. The high specificity and sensitivity of PGE/NiTsPc-ZnONPs-CNT for DA enabled its direct detection in human serum without sample pretreatment as well as in DA-enriched serum samples, whose recovery levels were close to 100%, thereby confirming the effectiveness of the proposed method. In general, PGE/NiTsPc-ZnONPs-CNT is a promising candidate for future applications in clinical diagnosis.

Activation of transient receptor potential vanilloid channel 4 contributes to the development of ethanol-induced gastric injury in mice.

The transient receptor potential vanilloid channel 4 (TRPV4) is associated with the development of several pathologies, particularly gastric disorders. However, there are no studies associating this receptor with the pathophysiology of gastric erosions. The aim of this study was to investigate the role of TRPV4 in the development of ethanol-induced gastric damage in vivo. Gastric lesions were induced by ethanol in Swiss mice pretreated with TRPV4 antagonists, GSK2193874 (0.1; 0.3 and 0.9 mg/kg) or Ruthenium red (0.03; 0.1 or 0.3 mg/kg) or its agonist, GSK1016790A (0.9 mg/kg). Gastric mucosal samples were taken for histopathology, immunohistochemistry, atomic force microscopy and evaluation of antioxidant parameters. The gastric mucus content and TRPV4 mRNA expression were analyzed. Ethanol exposure induced upregulation of gastric mRNA and protein expression of TRPV4. TRPV4 blockade promoted gastroprotection against ethanol-induced injury on macro- and microscopic levels, leading to reduced hemorrhage, cell loss and edema and enhanced gastric mucosal integrity. Moreover, an increase in superoxide dismutase (SOD) and glutathione (GSH) activity was observed, followed by a decrease in malondialdehyde (MDA) levels. TRPV4 blockade during alcohol challenge reestablished gastric mucus content. The combination of TRPV4 agonist and ethanol revealed macroscopic exacerbation of gastric damage area. Our results confirmed the association of TRPV4 with the development of gastric injury, showing the importance of this receptor for further investigations in the field of gastrointestinal pathophysiology and pharmacology.

Insights into the Antimicrobial Activity of Hydrated Cobaltmolybdate Doped with Copper.

Molybdates are biocidal materials that can be useful in coating surfaces that are susceptible to contamination and the spread of microorganisms. The aim of this work was to investigate the effects of copper doping of hydrated cobalt molybdate, synthesized by the co-precipitation method, on its antibacterial activity and to elucidate the structural and morphological changes caused by the dopant in the material. The synthesized materials were characterized by PXRD, Fourier Transformed Infrared (FTIR), thermogravimetric analysis/differential scanning calorimetry (TG/DSC), and SEM-Energy Dispersive Spectroscopy (SEM-EDS). The antibacterial response of the materials was verified using the Minimum Inhibitory Concentration (MIC) employing the broth microdilution method. The size of the CoMoO4·1.03H2O microparticles gradually increased as the percentage of copper increased, decreasing the energy that is needed to promote the transition from the hydrated to the beta phase and changing the color of material. CoMoO4·1.03H2O obtained better bactericidal performance against the tested strains of Staphylococcus aureus (gram-positive) than Escherichia coli (gram-negative). However, an interesting point was that the use of copper as a doping agent for hydrated cobalt molybdate caused an increase of MIC value in the presence of E. coli and S. aureus strains. The study demonstrates the need for caution in the use of copper as a doping material in biocidal matrices, such as cobalt molybdate.

Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons.

Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.

Biopolymer Extracted from Anadenanthera colubrina (Red Angico Gum) Exerts Therapeutic Potential in Mice: Antidiarrheal Activity and Safety Assessment.

Anadenanthera colubrina var. cebil (Griseb.) Altschul (Fabaceae family), commonly known as the red angico tree, is a medicinal plant found throughout Brazil's semi-arid area. In this study, a chemical analysis was performed to investigate the antidiarrheal activity and safety profile of red angico gum (RAG), a biopolymer extracted from the trunk exudate of A. colubrina. Upon FT-IR spectroscopy, RAG showed bands in the regions of 1608 cm-1, 1368 cm-1, and 1029 cm-1, which relate to the vibration of O-H water molecules, deformation vibration of C-O bands, and vibration of the polysaccharide C-O band, respectively, all of which are relevant to glycosidic bonds. The peak molar mass of RAG was 1.89 × 105 g/mol, with the zeta potential indicating electronegativity. RAG demonstrated high yield and solubility with a low degree of impurity. Pre-treatment with RAG reduced the total diarrheal stool and enteropooling. RAG also enhanced Na+/K+-ATPase activity and reduced gastrointestinal transit, and thereby inhibited intestinal smooth muscle contractions. Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that RAG can interact with GM1 receptors and can also reduce E. coli-induced diarrhea in vivo. Moreover, RAG did not induce any signs of toxicity in mice. These results suggest that RAG is a possible candidate for the treatment of diarrheal diseases.

Quaternization of angico gum and evaluation of anti-staphylococcal effect and toxicity of their derivatives.

Modified polysaccharides have been featured as new agents against bacterial infection presenting biocompatibility in their use for medical purposes. In this work, we carried out the quaternization of Angico gum (AG). Quaternized Angico gum derivatives (QAG) were produced using a cationic moiety (3-Chloro-2-hydroxypropyl)trimethylammonium chloride onto the gum backbone. The products were characterized by FT-IR spectroscopy, Zeta potential, elemental analysis, and 1H NMR and degree of substitution (DS) was calculated. QAG were also evaluated for their anti-staphylococcal activity by determining Minimum Inhibitory and Bactericidal concentrations against pathogenic Staphylococcus spp. and by imaging using Atomic Force Microscopy. The hemolysis test and Galleria mellonella model were used to assess toxicity of gums. Our results showed that derivatives who presented highest DS (QAG-A3, 0.48 and QAG-B, 0.54) showed more effective antibacterial activity against tested bacteria, biocompatibility with erythrocytes and non-toxicity in G. mellonella model.

Alendronate-induced gastric damage in normoglycemic and hyperglycemic rats is reversed by metformin.

Alendronate is a bisphosphonate widely used for the treatment of osteoporosis; however, one of its main adverse reactions is gastric ulcer. Metformin is an oral antihyperglycemic agent that has several beneficial effects, including healing, gastroprotective and anti-tumoral action. This study aimed to evaluate the gastroprotective activity of metformin in alendronate-induced gastric damage in normoglycemic and hyperglycemic rats. The treatment with 100 mg/kg of metformin showed a significant gastroprotective effect in damage induced by alendronate (50 mg/kg) in macroscopic analysis and the analysis of light microscopy and atomic force microscopy. The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-α, IL-1ß and IL-6), myeloperoxidase activity, and malondialdehyde levels. Also, the results suggested that metformin induces the maintenance of basal levels of collagen and increase the production of mucus. Interestingly, with the presence of the AMPK inhibitor (Compound C), metformin presented impairment of its gastroprotective action. The gastroprotective effect of metformin might be related to the activation of the AMPK pathway. These findings revealed that metformin has a gastroprotective action and may be considered a therapeutic potential for the prevention and treatment of gastric lesions induced by alendronate.

Carvacryl acetate, a novel semisynthetic monoterpene ester, binds to the TRPA1 receptor and is effective in attenuating irinotecan-induced intestinal mucositis in mice.

OBJECTIVES: We aimed to determine whether carvacryl acetate acts as a TRPA1 receptor agonist and its effects against irinotecan (CPT-11) induced intestinal mucositis in mice. METHODS: TRPA1 structure was obtained from a protein databank, and the 3D structure of carvacryl acetate was determined. Appropriate binding conformations were discovered via automatic docking simulations. To determine the effect of carvacryl acetate in vivo, mice were treated with either DMSO 2%, CPT-11, carvacryl acetate followed by CPT-11, or HC-030031, a TRPA1 antagonist, followed by carvacryl acetate. Jejunum samples were taken and structural, inflammatory and antioxidant parameters were studied. KEY FINDINGS: Eight amino acids residues in TRPA1 established stable interactions with carvacryl acetate, which led to pharmacological efficacy against CPT-11-induced intestinal mucositis via reduction of both neutropenia and bacteremia, increase in villi height and crypt depth, decrease in pro-inflammatory cytokines (interleukin-1ß, keratinocyte chemoattractant and tumour necrosis factor-α) and decrease in malondialdehyde and nitric oxide metabolite levels in the jejunum. CONCLUSIONS: Carvacryl acetate is a promising anti-inflammatory and antioxidant agent, a fact confirmed through observations of its interactions with TRPA1 in CPT-11-induced intestinal mucositis in mice.

Anti-inflammatory effect of the monoterpene myrtenol is dependent on the direct modulation of neutrophil migration and oxidative stress.

Myrtenol is a bicyclic monoterpene with anti-inflammatory properties. However, the mechanisms involved are partially unknown. Here, we investigated the effect of myrtenol during experimental chronic arthritis and the possible modulating activity of oxidative stress and neutrophil migration. Complete Freund's Adjuvant (CFA)-sensitized rats were treated with vehicle (1 mL/kg, po), myrtenol (12.5, 25 or 50 mg/kg, po), indomethacin (10 mg/kg, po) or dexamethasone (0.4 mg/kg) followed by intra-articular injection of CFA (0.5 mg/mL, 50 µL per joint). Then, paw edema and articular incapacitation (paw elevation time) were evaluated for 14 days. On the last day, a blood concentration superoxide dismutase (SOD) and nitrite was determined. In another experimental setting, human neutrophils were incubated with vehicle (sterile saline, 1 mL) or myrtenol (10-100 ng/mL) and the in vitro chemotaxis to N-formylmethionine-leucyl-phenylalanine (fMLP) (10-7 M/well) was evaluated. In addition, antiinflammatory effect of myrtenol was investigated in carrageenan-induced peritonitis. We found that CFA induced a prominent paw swelling and incapacitation of the joint, which were significantly prevented by myrtenol (P < 0.05). In addition, blood accumulation nitrite was attenuated by myrtenol when compared with vehicle-treated CFA group (P < 0.05). Furthermore, plasma levels of SOD were significantly increased by myrtenol versus vehicle-treated CFA group (P < 0.05). Moreover, fMLP-triggered neutrophil chemotaxis and carrageenan-induced peritonitis were markedly prevented by myrtenol (P < 0.05). Therefore, myrtenol showed anti-inflammatory and antinociceptive effects on experimental chronic arthritis, which seems to be related to the direct modulation of neutrophil migration and antioxidant activity.

Anti-diarrhoeal therapeutic potential and safety assessment of sulphated polysaccharide fraction from Gracilaria intermedia seaweed in mice.

Sulphated polysaccharides extracted from algae have been extensively studied for their diverse biological activities. Thus, the purpose of this study was to evaluate the chemical composition, the anti-diarrhoeal effect and acute toxicity of a sulphated polysaccharide fraction obtained from Gracilaria intermedia (SP-Gi). Initially, the FT-IR of SP-Gi revealed to be an agaran with sulphation at C-6 of the l-galactosyl residues. The anti-diarrhoeal activity of SP-Gi was evaluated in a castor oil-induced diarrhoea model. The effects of SP-Gi on enteropooling, Na +-K +-ATPase activity, gastrointestinal transit, and gastric emptying were then examined. Subsequently, the effect of SP-Gi on diarrhoea induced by cholera toxin (CT) and Escherichia coli was examined. In addition, an acute toxicity test was conducted in accordance with OECD guideline 423. Pre-treatment with SP-Gi reduces the total faeces, total diarrhoeal faeces, and enteropooling. SP-Gi (30mg/kg p.o.) increased Na+/K+-ATPase activity and reduced gastrointestinal transit through anticholinergic mechanisms. ELISA demonstrated that SP-Gi can interact with GM1 receptors and CT. SP-Gi reduced diarrhoea induced by E. coli and prevented weight loss in the animals. Moreover, SP-Gi did not induce any toxicity signs. These results suggest that SP-Gi is a possible candidate for the treatment of diarrhoeal illnesses.

Quaternized cashew gum: An anti-staphylococcal and biocompatible cationic polymer for biotechnological applications.

Chemical modifications to cashew gum (CG) structure have been previously reported to obtain new physicochemical characteristics, however until now there were no reports of modifications by introduction of new functional groups to add cationic character. This study presents a quaternization route for CG using a quaternary ammonium reagent. The chemical features of the quaternized cashew gum derivatives (QCG) were analyzed by: FTIR, elemental analysis, degree of substitution, Zeta potential, 1H NMR and 1H-13C correlation (HSQC). QCG were evaluated for their anti-staphylococcal activity by determining minimum inhibitory and bactericidal concentrations against pathogenic Staphylococcus spp. and by imaging using atomic force microscopy. Moreover, the mammalian cell biocompatibility were also assessed through hemolytic and cell toxicity assays. QCG presented promising antimicrobial activity against methicillin-resistant S. aureus and biocompatibility on tested cells. These results show that QCG could be a promising tool in the development of biomaterials with an anti-septic action.

Carvacrol reduces irinotecan-induced intestinal mucositis through inhibition of inflammation and oxidative damage via TRPA1 receptor activation.

Intestinal mucositis is an inflammatory process occurring in the intestinal mucosa and is a common side effect of irinotecan hydrochloride (CPT-11) based anticancer regimens. The transient receptor potential cation channel, subfamily A, member 1 (TRPA1) receptor is highly expressed in the intestinal mucosa and has the ability to identify cell damage signaling indicates its possible association with intestinal mucositis. Carvacrol is an agonist of the TRPA1 receptor and has anti-inflammatory properties. Thus, the aim of the present study was to verify the supposed anti-inflammatory and protective action of carvacrol via TRPA1 activation against intestinal mucositis induced by CPT-11 in mice. Briefly, mice were treated with either DMSO 2% or CPT-11 (75 mg/kg, per 4 days, i.p.) or the carvacrol (25, 75 or 150 mg/kg, per 8 days, i.p.) before CPT-11. In other group, the animals were pretreated with HC-030031, a TRPA1 antagonist, 30 min before treatment with carvacrol. On day 7, animal survival and bacteremia were assessed, and following euthanasia, samples of the jejunum were obtained for morphometric analysis and measurement of antioxidant and pro-inflammatory markers. Carvacrol was found to exert an anti-inflammatory action against CPT-11-induced intestinal mucositis through strong interactions with TRPA1 receptors; reduction in the production or release or both of pro-inflammatory cytokines (TNF-α, IL-1ß, and KC); and decrease in other indicators of inflammation (MPO, NF-κB, COX-2) and oxidative stress (GSH, MDA, and NOx levels). It also contributed to the restoration of the tissue architecture of the villi and crypts in the small intestine, and improved clinical parameters such as survival, body mass variation, leukogram, and blood bacterial count. Thus, TRPA1 could be a target for future therapeutic approaches in the treatment of intestinal mucositis.