Eugenia uniflora (pitanga) juice as a new alternative vehicle for Limosilactobacillus fermentum ATCC 23271: evaluation of antioxidant and anti-infective effects.

Probiotic-containing foods are among the most appreciated functional foods; however, probiotic-based dairy products cannot be consumed by people who are lactose intolerant, allergic to milk, or vegetarian or vegan individuals. Thus, new non-dairy matrices have been tested for probiotics delivery. This study evaluated the growth and viability of Limosilactobacillus fermentum ATCC 23271 and Lacticaseibacillus rhamnosus ATCC 9595 in Pitanga juice (Eugenia uniflora L.). The effects of the fermentation on the antioxidant and anti-infective properties of the juice were also analyzed. The E. uniflora juice allowed lactobacilli growth without supplementation, reaching rates around 8.4 Log CFU/mL and producing organic acids (pH values < 4) after 72 h of fermentation. The strain remained viable after 35 days of refrigerated storage. Fermentation by these bacteria increases the antioxidant capacity of the juice. The central composite rotational design was employed to evaluate the effects of bacterial inoculum and pulp concentration on growth and organic acids production by L. fermentum ATCC 23271. The strain was viable and produced organic acids in all tested combinations. L. fermentum-fermented juice and its cell-free supernatant significantly increased the survival of Tenebrio molitor larvae infected by enteroaggregative Escherichia coli 042. The results obtained in this study provide more insights into the potential of Pitanga juice to develop a functional non-dairy probiotic beverage with antioxidant and anti-infective properties.

Research Trends in Proteomic Studies Using Serum from COVID-19 Patients: A Bibliometric Analysis.

The COVID-19 pandemic significantly impacted the global populace, resulting in a staggering number of deaths across the globe. New approaches and biomarkers to evaluate disease progression are crucial for improving disease management. In this context, serum proteomics has emerged as a promising tool for identifying molecular alterations related to COVID-19. This work carried out a bibliometric evaluation of the current status and trends of studies applying serum proteomics to COVID-19 subjects. The search was performed using Web of Science and Scopus databases, and the results were analyzed in VOSviewer software. The investigation was limited to articles published between January 2020 and February 2023. The analysis found 48 articles, primarily experimental studies. China is the most influential country in this field, followed by the USA. The co-occurrence analysis performed by VOSviewer showed 170 keywords, of which 9 reached the occurrence threshold and were divided into two groups. The most cited words were related to biomarker identification and the use of proteomics for diagnosing and treating COVID-19. The most cited proteins include those classically associated with the immune system (IgG, IgM, interleukins, CXCL, CCL, MCP, CRP) and SAA1, SAA1, ApoA-1, TTR (prealbumin), SerpinA and ITIH4. Other studies have validated the predictive value of these serum markers and have the potential to improve the management of COVID-19 patients. The findings highlighted in this bibliometric study can help the researchers design new projects to enhance our understanding of the complex interplay between SARS-CoV-2 and host immunity.

Schinus terebinthifolius Leaf Lectin (SteLL) Reduces the Bacterial and Inflammatory Burden of Wounds Infected by Staphylococcus aureus Promoting Skin Repair.

Staphylococcus aureus is commonly found in wound infections where this pathogen impairs skin repair. The lectin isolated from leaves of Schinus terebinthifolius (named SteLL) has antimicrobial and antivirulence action against S. aureus. This study evaluated the effects of topical administration of SteLL on mice wounds infected by S. aureus. Seventy-two C57/BL6 mice (6−8 weeks old) were allocated into four groups: (i) uninfected wounds; (ii) infected wounds, (iii) infected wounds treated with 32 µg/mL SteLL solution; (iv) infected wounds treated with 64 µg/mL SteLL solution. The excisional wounds (64 mm2) were induced on the dorsum and infected by S. aureus 432170 (4.0 × 106 CFU/wound). The daily treatment started 1-day post-infection (dpi). The topical application of both SteLL concentrations significantly accelerated the healing of S. aureus-infected wounds until the 7th dpi, when compared to untreated infected lesions (reductions of 1.95−4.55-fold and 1.79−2.90-fold for SteLL at 32 µg/mL and 64 µg/mL, respectively). The SteLL-based treatment also amended the severity of wound infection and reduced the bacterial load (12-fold to 72-fold for 32 µg/mL, and 14-fold to 282-fold for 64 µg/mL). SteLL-treated wounds show higher collagen deposition and restoration of skin structure than other groups. The bacterial load and the levels of inflammatory markers (IL-6, MCP-1, TNF-α, and VEGF) were also reduced by both SteLL concentrations. These results corroborate the reported anti-infective properties of SteLL, making this lectin a lead candidate for developing alternative agents for the treatment of S. aureus-infected skin lesions.

Antimicrobial and anti-inflammatory effects of Eugenia brejoensis essential oil in mice wounds infected by Staphylococcus aureus.

Eugenia brejoensis Mazine (Myrtaceae) is source of an essential oil (EbEO) with anti-infective activities against Staphylococcus aureus. This study evaluated the antimicrobial and anti-inflammatory potentials of EbEO in S. aureus-infected skin wounds. The excisional lesions (64 mm2) were induced on Swiss mice back (6 to 8-week-old) that were allocated into 3 groups (n = 12): 1) non-infected wounds (CON); 2) wounds infected with S. aureus ATCC 6538 (Sa); 3) S. aureus-infected wounds and treated with EbEO (Sa + EbEO). The infected groups received approximately 104 CFU/wound. The animals were treated with EbEO (10 µg/wound/day) or vehicle from the 1-day post-infection (dpi) until the 10th dpi. The clinical parameters (wound area, presence of exudate, edema intensity, etc.) were daily analyzed. The levels of inflammatory mediators (cytokines, nitric oxide, VEGF) and bacterial load were measured at the cutaneous tissue at 4th dpi and 10th dpi. Topical application of EbEO accelerated wound contraction with an average contraction of 83.48 ± 11.27 % of the lesion area until 6th dpi. In this period, the rates of lesion contraction were 54.28 ± 5.57% and 34.5 ± 2.67% for CON and Sa groups, respectively. The positive effects of EbEO on wound contraction were associated with significantly (p < 0.05) reduction on bacterial load and the release of inflammatory mediators (IL-6, IL-17A, TNF-α, NO and VEGF). Taken together, these data confirm the antimicrobial potential of EbEO and provide insights into its anti-inflammatory effects, making this essential oil an interesting candidate for the development of new therapeutic alternatives for infected cutaneous wounds.

Development and Physicochemical Characterization of Eugenia brejoensis Essential Oil-Doped Dental Adhesives with Antimicrobial Action towards Streptococcus mutans.

Dental caries is a multifactorial, biofilm-dependent infectious disease that develops when detrimental changes occur in the oral cavity microenvironment. The antimicrobial and antivirulence properties of the essential oil obtained from the leaves of Eugenia brejoensis Mazine (EBEO) have been reported against Gram-positive and Gram-negative bacteria. Herein, the antimicrobial action of EBEO towards Streptococcus mutans is reported, along with the development and characterization of dental adhesives doped with. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EBEO were determined against S. mutans, while its toxicity was analyze using Tenebrio molitor larvae. EBEO (MIC and 10×MIC) was incorporated into the Ambar Advanced Polymerization System® (Ambar APS), a two-step total-etch adhesive system (FGM Dental Group), and the antibiofilm action was evaluated. The reflective strength, modulus of elasticity, degree of conversion, and maximum rate of polymerization of each adhesive were also determined. The MIC and MBC values of EBEO against S. mutans were 62.5 µg/mL. The tested concentrations of EBEO were non-toxic to T. molitor larvae. The formation of S. mutans biofilms was significantly inhibited by EBEO and EBEO-coated resin discs (p < 0.05). Importantly, EBEO incorporation did not affect the mechanical and physicochemical properties in relation to oil-free adhesive version. EBEO showed strong antibacterial and antibiofilm activity against S. mutans, no toxicity effect against T. molitor larvae, and did not jeopardize the physical-chemical properties tested.

Optimization of Osmotic Dehydration of Sapodilla (Achras zapota L.).

Sapodilla (Achras zapota L.) is a fruit with a great nutritional potential; however, its perishable nature is a great obstacle for commercialization/exportation. Herein, osmotic dehydration was applied to sapodilla to reduce post-harvest losses and obtain a stable product with acceptable sensorial characteristics. Initially, a 2³ full-factorial design was performed to determine the effect of temperature (30−50 °C), sucrose concentration (40−60% °Brix) and immersion time (90−240 min) on the moisture loss (ML), solid gain (SG) and dehydration efficiency index (DEI). The samples with higher DEI values were subjected to sensory analysis, followed by physicochemical, microbiological and structural analyses. The temperature and the concentration of the osmotic solution had significant influence (p < 0.05) on ML and SG, whereas DEI was significantly influenced (p < 0.05) by the concentration of osmotic solution and the immersion time. The sample produced by osmotic dehydration using the optimized conditions (40 °C, 50 °Brix; 165 min) obtained higher scores on the sensorial attributes, greater compliance with microbiological standards and generated turgor reduction and ruptures of sapodilla cell walls.

Immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by Staphylococcus aureus.

This work evaluated the immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by S. aureus. Swiss mice were divided into 3 groups (n = 12/group): non-inoculated (Control group); inoculated with S. aureus (Sa group); inoculated with S. aureus and treated with Cramoll (Sa + Cramoll group). In each animal, one lesion (64 mm2) was induced on the back and contaminated with S. aureus (~4.0 × 106 CFU/wound). The treatment with Cramoll (5 µg/animal/day) started 1-day post-infection (dpi) and extended for 10 days. Clinical parameters (wound size, inflammatory aspects, etc.) were daily recorded; while cytokines levels, bacterial load and histological aspects were determined in the cutaneous tissue at 4th dpi or 11th dpi. The mice infected with S. aureus exhibited a delay in wound contraction and the highest inflammatory scores. These effects were impaired by the treatment with Cramoll which reduced the release of key inflammatory mediators (TNF-α, NO, VEGF) and the bacterial load at wound tissue. Histological evaluations showed a restauration of skin structures in the animals treated with Cramoll. Taken together, these results provide more insights about the healing and immunomodulatory properties of Cramoll and suggest this lectin as a lead compound for treatment of wound infection.

Evaluation of Growth, Viability, Lactic Acid Production and Anti-Infective Effects of Lacticaseibacillus rhamnosus ATCC 9595 in Bacuri Juice (Platonia insignis).

Fruit juices have been emerging as excellent vehicles for development of probiotic products due to their nutritional properties and presence of bioactive compounds. This work evaluated the growth and viability of Limosilactobacillus fermentum ATCC 23271 and Lacticaseibacillus rhamnosus ATCC 9595 in bacuri juice (Platonia insignis Mart., Clusiaceae). Both strains were able to grow in bacuri juice, without any supplementation. Viability was kept after 28 days of storage; however, growth was significantly higher for L. rhamnosus ATCC 9595 (7.40 ± 0.04 Log CFU/mL). Following this, the effects of bacterial inoculum and pulp concentration on growth and lactic acid production by L. rhamnosus ATCC 9595 were investigated using a central composite rotational design. The inoculum concentration was the main factor for obtaining the most favorable relation between growth and organic acid production (G/pH ratio). Among the tested conditions, those used in assay 6 allowed the best G/pH ratio (2.13) and higher lactic acid production (4.14 g/L). In these conditions, L. rhamnosus ATCC 9595 grown in bacuri juice showed the same resistance towards acidification or addition of lysozyme than when cultivated in MRS. Finally, the anti-infective effects of fermented and non-fermented juices were analyzed using Tenebrio molitor larvae infected by enteroaggregative Escherichia coli 042. The pre-treatment with supernatants of both fermented and non-fermented juices significantly increased the survival of E. coli-infected larvae. However, only the L. rhamnosus-fermented juice had protective effects when inoculated 2 h after infection. Collectively, the results obtained in this research allowed the basis for the development of a non-dairy probiotic product from bacuri juice.

Interplay between ESKAPE Pathogens and Immunity in Skin Infections: An Overview of the Major Determinants of Virulence and Antibiotic Resistance.

The skin is the largest organ in the human body, acting as a physical and immunological barrier against pathogenic microorganisms. The cutaneous lesions constitute a gateway for microbial contamination that can lead to chronic wounds and other invasive infections. Chronic wounds are considered as serious public health problems due the related social, psychological and economic consequences. The group of bacteria known as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp.) are among the most prevalent bacteria in cutaneous infections. These pathogens have a high level of incidence in hospital environments and several strains present phenotypes of multidrug resistance. In this review, we discuss some important aspects of skin immunology and the involvement of ESKAPE in wound infections. First, we introduce some fundamental aspects of skin physiology and immunology related to cutaneous infections. Following this, the major virulence factors involved in colonization and tissue damage are highlighted, as well as the most frequently detected antimicrobial resistance genes. ESKAPE pathogens express several virulence determinants that overcome the skin's physical and immunological barriers, enabling them to cause severe wound infections. The high ability these bacteria to acquire resistance is alarming, particularly in the hospital settings where immunocompromised individuals are exposed to these pathogens. Knowledge about the virulence and resistance markers of these species is important in order to develop new strategies to detect and treat their associated infections.

Chemical composition, antioxidant and antiprotozoal activity of Eugenia gracillima Kiaersk. leaves essential oil.

This work evaluated the volatile composition, antioxidant and antiprotozoal activities of the essential oil obtained from leaves of Eugenia gracillima Kiaersk. (EGEO) grown in Brazilian Northeast area (Araripe, Brazil). The volatile compounds of EGEO were analyzed by GC and GC-MS and its chemical composition is mainly composed of sesquiterpene hydrocarbons (91.22%), oxygenated sesquiterpenes (7.45%) and monoterpene (1.01%). The most abundant volatile constituents of the EGEO were germacrene D (16.10%), γ-muurolene (15.60%), bicyclogermacrene (8.53%), germacrene B (7.43%), and Δ-elemene (6.06%). The oil showed weak to moderate antioxidant activity. EGEO was highly selective to Leishmania braziliensis and Leishmania infantum promastigotes with selective indexes of 73.66 and 71.41, respectively. EGEO did not inhibit Trypanosoma cruzi. These data suggest that the E. gracillima essential oil is a relevant source of lead compounds for development of anti-Leishmania drugs.

Exploring lectin-glycan interactions to combat COVID-19: Lessons acquired from other enveloped viruses.

The emergence of a new human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed great pressure on the health system worldwide. The presence of glycoproteins on the viral envelope opens a wide range of possibilities for the application of lectins to address some urgent problems involved in this pandemic. In this work, we discuss the potential contributions of lectins from nonmammalian sources in the development of several fields associated with viral infections, most notably COVID-19. We review the literature on the use of nonmammalian lectins as a therapeutic approach against members of the Coronaviridae family, including recent advances in strategies of protein engineering to improve their efficacy. The applications of lectins as adjuvants for antiviral vaccines are also discussed. Finally, we present some emerging strategies employing lectins for the development of biosensors, microarrays, immunoassays and tools for purification of viruses from whole blood. Altogether, the data compiled in this review highlight the importance of structural studies aiming to improve our knowledge about the basis of glycan recognition by lectins and its repercussions in several fields, providing potential solutions for complex aspects that are emerging from different health challenges.

Compounds isolated from Bixa orellana: evidence-based advances to treat infectious diseases / Compuestos aislados de Bixa orellana: avances basados en la evidencia para tratar enfermedades infecciosas

SUMMARY Bixa orellana L. is a native plant from Brazil, but it is also present in other tropical countries such as Peru, Colombia, Ecuador, Mexico, Indonesia, India and East Africa. It is popularly known as Urucum in Brazil. This review shows the potential of bioactive compounds derived from B. orellana to treat infectious diseases due their antimicrobial and antioxidant properties. This plant is also related as an antiinflammatory agent for treatment of pulmonary diseases, or even as eye drops for redness. Its leaves are used for treatment of snakebite, diarrhea, gonorrhea, hepatitis, gastritis, diuretic, antipyretic, and for skin disease. This popular knowledge has encouraged the identification of bioactive compounds in this plant. Compounds as β-cryptoxanthin, geranylgeraniol, lutein, procyanidin B2, procyanidin B3, ellagi tannin isomer and ellagic acid deoxyhexose have been described. These compounds inhibited pathogenic microorganisms such as bacteria, fungi, protozoan and viruses. In addition, some compounds with anti-inflammatory and antioxidant activities were also described. In this sense, B. orellana is a promising source of compounds that could be applied in antimicrobial therapy. This review work may help in the understanding and incentive of new research for antimicrobial discoveries using different B. orellana compounds.

RESUMEN Bixa orellana L. es una planta nativa de Brasil, pero también está presente en otros países tropicales como Perú, Colombia, Ecuador, México, Indonesia, India y África Oriental. Es conocida popularmente como Urucum en Brasil. Esta revisión expone el potencial de los compuestos bioactivos derivados de B. orellana para tratar enfermedades debido a sus propiedades antimicrobianas y antioxidantes. Esta planta también está relacionada como un agente antiinflamatorio para el tratamiento de enfermedades pulmonares e incluso como gotas para los ojos para el enrojecimiento. Sus hojas se utilizan para el tratamiento de la mordedura de serpiente, diarrea, gonorrea, hepatitis, gastritis, diuréticos, antipiréticos y para enfermedades de la piel. Ese conocimiento popular ha fomentado la identificación de compuestos bioactivos en esa planta. Los compuestos β-criptoxantina, geranilgeraniol, luteína, procianidina B2, procianidina B3, isómero elagitanino y ácido elágico desoxihexosa inhibieron microorganismos patógenos como bacterias, hongos, protozoos y virus. En ese sentido, B. orellana es una fuente prometedora de compuestos que podrían aplicarse en la terapia antimicrobiana. Este trabajo de revisión puede ayudar a comprender e incentivar nuevas investigaciones para los descubrimientos de antimicrobianos que utilizan diferentes compuestos de B. orellana.

Products Derived from Buchenavia tetraphylla Leaves Have In Vitro Antioxidant Activity and Protect Tenebrio molitor Larvae against Escherichia coli-Induced Injury.

The relevance of oxidative stress in the pathogenesis of several diseases (including inflammatory disorders) has traditionally led to the search for new sources of antioxidant compounds. In this work, we report the selection of fractions with high antioxidant action from B. tetraphylla (BT) leaf extracts. In vitro methods (DPPH and ABTS assays; determination of phenolic and flavonoid contents) were used to select products derived from B. tetraphylla with high antioxidant action. Then, the samples with the highest potentials were evaluated in a model of injury based on the inoculation of a lethal dose of heat-inactivated Escherichia coli in Tenebrio molitor larvae. Due to its higher antioxidant properties, the methanolic extract (BTME) was chosen to be fractionated using Sephadex LH-20 column-based chromatography. Two fractions from BTME (BTFC and BTFD) were the most active fractions. Pre-treatment with these fractions protected larvae of T. molitor from the stress induced by inoculation of heat-inactivated E. coli. Similarly, BTFC and BTFD increased the lifespan of larvae infected with a lethal dose of enteroaggregative E. coli 042. NMR data indicated the presence of aliphatic compounds (terpenes, fatty acids, carbohydrates) and aromatic compounds (phenolic compounds). These findings suggested that products derived from B. tetraphylla leaves are promising candidates for the development of antioxidant and anti-infective agents able to treat oxidative-related dysfunctions.

Schinus terebinthifolia leaf lectin (SteLL) has anti-infective action and modulates the response of Staphylococcus aureus-infected macrophages.

Staphylococcus aureus is recognized as an important pathogen causing a wide spectrum of diseases. Here we examined the antimicrobial effects of the lectin isolated from leaves of Schinus terebinthifolia Raddi (SteLL) against S. aureus using in vitro assays and an infection model based on Galleria mellonella larvae. The actions of SteLL on mice macrophages and S. aureus-infected macrophages were also evaluated. SteLL at 16 µg/mL (8 × MIC) increased cell mass and DNA content of S. aureus in relation to untreated bacteria, suggesting that SteLL impairs cell division. Unlike ciprofloxacin, SteLL did not induce the expression of recA, crucial for DNA repair through SOS response. The antimicrobial action of SteLL was partially inhibited by 50 mM N-acetylglucosamine. SteLL reduced staphyloxathin production and increased ciprofloxacin activity towards S. aureus. This lectin also improved the survival of G. mellonella larvae infected with S. aureus. Furthermore, SteLL induced the release of cytokines (IL-6, IL-10, IL-17A, and TNF-α), nitric oxide and superoxide anion by macrophagens. The lectin improved the bactericidal action of macrophages towards S. aureus; while the expression of IL-17A and IFN-γ was downregulated in infected macrophages. These evidences suggest SteLL as important lead molecule in the development of anti-infective agents against S. aureus.

Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus.

The occurrence of damage on bacterial DNA (mediated by antibiotics, for example) is intimately associated with the activation of the SOS system. This pathway is related to the development of mutations that might result in the acquisition and spread of resistance and virulence factors. The inhibition of the SOS response has been highlighted as an emerging resource, in order to reduce the emergence of drug resistance and tolerance. Herein, we evaluated the ability of betulinic acid (BA), a plant-derived triterpenoid, to reduce the activation of the SOS response and its associated phenotypic alterations, induced by ciprofloxacin in Staphylococcus aureus. BA did not show antimicrobial activity against S. aureus (MIC > 5000 µg/mL), however, it (at 100 and 200 µg/mL) was able to reduce the expression of recA induced by ciprofloxacin. This effect was accompanied by an enhancement of the ciprofloxacin antimicrobial action and reduction of S. aureus cell volume (as seen by flow cytometry and fluorescence microscopy). BA could also increase the hyperpolarization of the S. aureus membrane, related to the ciprofloxacin action. Furthermore, BA inhibited the progress of tolerance and the mutagenesis induced by this drug. Taken together, these findings indicate that the betulinic acid is a promising lead molecule in the development helper drugs. These compounds may be able to reduce the S. aureus mutagenicity associated with antibiotic therapies.

Anti-staphylococcal activity of Syagrus coronata essential oil: Biofilm eradication and in vivo action on Galleria mellonela infection model.

In this study, essential oil extracted from Syagrus coronata seeds (SCEO) was evaluated for antibacterial and antibiofilm activities against Staphylococcus aureus; in addition, Galleria mellonella model was used as an in vivo infection model. SCEO was mainly composed by fatty acids (89.79%) and sesquiterpenes (8.5%). The major components were octanoic acid, dodecanoic acid, decanoic acid and γ-eudesmol. SCEO showed bactericidal activity (minimal bactericidal concentration from 312 to 1250 µg/mL) against all tested S. aureus clinical isolates, which showed distinct biofilm-forming and multiple drug resistance phenotypes. SCEO weakly reduced biomass but remarkably decreased cell viability in pre-formed biofilms of S. aureus isolate UFPEDA-02 (ATCC-6538). Electron microscopy analysis showed that SCEO treatments decreased the number of bacterial cells (causing structural alterations) and lead to loss of the roughness in the multiple layers of the three-dimensional biofilm structure. In addition, overproduction of exopolymeric matrix was observed. SCEO at 31.2 mg/kg improved the survival of G. mellonela larvae inoculated with UFPEDA-02 isolate and reduced the bacterial load in hemolymph and melanization. In conclusion, SCEO is an antibacterial agent against S. aureus strains with different resistance phenotypes and able to disturb biofilm architecture. Our results show SCEO as a potential candidate to drug development.

Polysaccharide-Based Formulations for Healing of Skin-Related Wound Infections: Lessons from Animal Models and Clinical Trials.

Skin injuries constitute a gateway for pathogenic bacteria that can be either part of tissue microbiota or acquired from the environmental. These microorganisms (such as Acinetobacter baumannii, Enterococcus faecalis,Pseudomonas aeruginosa, and Staphylococcus aureus) produce virulence factors that impair tissue integrity and sustain the inflammatory phase leading for establishment of chronic wounds. The high levels of antimicrobial resistance have limited the therapeutic arsenal for combatting skin infections. Thus, the treatment of non-healing chronic wounds is a huge challenge for health services worldwide, imposing great socio-economic damage to the affected individuals. This scenario has encouraged the use of natural polymers, such as polysaccharide, in order to develop new formulations (membranes, nanoparticles, hydrogels, scaffolds) to be applied in the treatment of skin infections. In this non-exhaustive review, we discuss the applications of polysaccharide-based formulations in the healing of infected wounds in animal models and clinical trials. The formulations discussed in this review were prepared using alginate, cellulose, chitosan, and hyaluronic acid. In addition to have healing actions per se, these polysaccharide formulations can act as transdermal drug delivery systems, controlling the release of active ingredients (such as antimicrobial and healing agents). The papers show that these polysaccharides-based formulations are efficient in controlling infection and improve the healing, even in chronic infected wounds. These data should positively impact the design of new dressings to treat skin infections.

Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund's Adjuvant-Induced Mono-Arthritis.

Rheumatoid arthritis (RA) is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN) is a natural compound that has been suggested as an antioxidant. Here, SFN's effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund's Adjuvant (CFA-10 µg/joint, in 10 µL) into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg) or vehicle (3% DMSO in saline), intraperitoneally (i.p.), twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR) activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C⁺ and Ly6G⁺ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G⁺ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

Virtual Screening for the Development of New Effective Compounds Against Staphylococcus aureus.

Staphylococcus aureus is a notorious pathogenic bacterium causing a wide range of diseases from soft-tissue contamination, to more serious and deep-seated infections. This species is highlighted by its ability to express several kinds of virulence factors and to acquire genes related to drug resistance. Target this number of factors to design any drug is not an easy task. In this review, we discuss the importance of computational methods to impulse the development of new drugs against S. aureus. The application of docking methods to screen large libraries of natural or synthetic compounds and to provide insights into action mechanisms is demonstrated. Particularly, the studies that validated in silico results with biochemical and microbiological assays are highlighted. We also comment on the computer-aided design of new molecules using some known inhibitors. The confirmation of in silico results with biochemical and microbiological assays allowed the identification of lead molecules that could be used for drug design such as rhodomyrtone, quinuclidine, berberine (and their derivative compounds). The fast development of the computational methods is essential to improve our ability to discover new drugs, as well as to expand understanding about drug-target interactions.