Direct Antimicrobial Effects Research Articles

New LsrK Ligands as AI-2 Quorum Sensing Interfering Compounds against Biofilm Formation.

Antimicrobial resistance (AMR) represents a critical global health crisis. An innovative strategy to deal with AMR is to interfere with biofilm formation and bacterial quorum sensing (QS). In this study, newly designed autoinducer-2 (AI-2)-inspired compounds in targeting biofilm-associated infections were evaluated for their ability to inhibit biofilm formation in Staphylococcus aureus and Pseudomonas aeruginosa. The most effective compounds, 5d, 5e, and 7b, exhibited potent antibiofilm activity with minimal inhibitory concentrations in the low microgram per mL range. Detailed biological assays confirmed that the antibiofilm activity was primarily driven through AI-2 QS inhibition rather than direct antimicrobial effects. The combination of different spectroscopic techniques, such as differential scanning fluorimetry, intrinsic tryptophan fluorescence, circular dichroism, and nuclear magnetic resonance, elucidated the binding between the compounds and the LsrK enzyme, a key player in AI-2 mediated QS. Our findings highlight the potential of these novel QS inhibitors as promising therapeutic agents against biofilm-associated infections.

Immunoglobulin Replacement Therapy: Insights into Multiple Myeloma Management.

Immunoglobulin (Ig) replacement therapy (IgRT) consists of the administration of low-dose human polyclonal Igs for the treatment of primary and secondary hypogammaglobulinemia that are associated with recurrent infections and immune dysfunction. IgRT restores physiological antibody levels and induces an immunomodulatory effect by strengthening immune effector cells, thus reducing infections. Here, we describe the pharmacology of different Ig formulations with a particular focus on their mechanism of action as low-dose IgRT, including the direct anti-microbial effect and the immunomodulatory function. In addition, we describe the use of therapeutic Igs for the management of multiple myeloma (MM), a hematologic malignancy characterized by severe secondary hypogammaglobulinemia associated with poor patient outcome. In MM settings, IgRT prevents life-threatening and recurrent infections showing promising results regarding patient survival and quality of life. Nevertheless, the clinical benefits of IgRT are still controversial. A deeper understanding of the immune-mediated effects of low-dose IgRT will provide the basis for novel combined therapeutic options and personalized therapy in MM and other conditions characterized by hypogammaglobulinemia.

Lactobacilli decrease the susceptibility of Salmonella Typhimurium to azithromycin.

Bacteria are involved in numerous interactions during infection and among host-associated microbial populations. Salmonella enterica serovar Typhimurium is a foodborne pathogen of great importance as well as a model organism to study interactions within a microbial community. In this study, we found that S. Typhimurium becomes tolerant to azithromycin when co-cultured with lactobacilli strains. Similarly, acidified media, from cell-free supernatant of lactobacilli cultures for instance, also induced the tolerance of S. Typhimurium to azithromycin. The addition of membrane disruptors restored the normal sensitivity to azithromycin in acidified media, but not when lactobacilli were present. These results suggested that the acidification of the media led to modification in envelope homeostasis, but that a different mechanism promoted the tolerance to azithromycin in the presence of lactobacilli strains. To further understand how lactobacilli strains modify the sensitivity of S. Typhimurium to azithromycin, a high-throughput assay was performed using the single-gene deletion collection of the S. Typhimurium (1) in co-culture with Lacticaseibacillus rhamnosus and (2) in sterile acidic conditions (pH 5.5 media only). As expected, both screens identified genes involved in envelope homeostasis and membrane permeability. Our results also suggest that changes in the metabolism of S. Typhimurium induce the tolerance observed in the presence of L. rhamnosus. Our results thus highlight two different mechanisms by which lactobacilli induce the tolerance of S. Typhimurium to azithromycin.IMPORTANCEThis study provides valuable insights into the intricate interactions between bacteria during infections and within host-associated microbial communities. Specifically, it sheds light on the significant role of lactobacilli in inducing antibiotic tolerance in Salmonella enterica serovar Typhimurium, a critical foodborne pathogen and model organism for microbial community studies. The findings not only uncover the mechanisms underlying this antibiotic tolerance but also reveal two distinct pathways through which strains of lactobacilli might influence Salmonella's response to antibiotics. Understanding these mechanisms has the potential to enhance our knowledge of bacterial infections and may have implications for the development of strategies to combat antibiotic resistance in pathogens, such as Salmonella. Furthermore, our results underscore the necessity to explore beyond the direct antimicrobial effects of antibiotics, emphasizing the broader microbial community context.

Antimicrobial Peptides (AMPs) and the Microbiome in Preterm Infants: Consequences and Opportunities for Future Therapeutics.

Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs play essential roles in various physiological processes. They induce angiogenesis, promote wound healing, modulate immune responses, and serve as chemoattractants for immune cells. AMPs regulate the microbiome and combat microbial infections on the skin, lungs, and gastrointestinal tract. Produced in response to microbial signals, AMPs help maintain a balanced microbial community and provide a first line of defense against infection. In preterm infants, alterations in microbiome composition have been linked to various health outcomes, including sepsis, necrotizing enterocolitis, atopic dermatitis, and respiratory infections. Dysbiosis, or an imbalance in the microbiome, can alter AMP profiles and potentially lead to inflammation-mediated diseases such as chronic lung disease and obesity. In the following review, we summarize what is known about the vital role of AMPs as multifunctional peptides in protecting newborn infants against infections and modulating the microbiome and immune response. Understanding their roles in preterm infants and high-risk populations offers the potential for innovative approaches to disease prevention and treatment.

Control of Peach Leaf Curl with Foliar Applications of Plant Immunity Inducers and Insights in Elicitation of Defense Responses against Taphrina deformans.

Taphrina deformans is the causal agent of leaf curl, a serious peach disease which causes significant losses in peach production worldwide. Nowadays, in order to control plant diseases, it is necessary to adopt novel and low-cost alternatives to conventional chemical fungicides. These promising strategies are targeted at eliciting host defense mechanisms via priming the host through the consecutive application of plant immunity inducers prior to pathogen challenge. In this study, we investigated whether chitosan or yeast cell wall extracts could provide enhanced tolerance against leaf curl in two-season field trials. Furthermore, we addressed the possible molecular mechanisms involved beyond the priming of immune responses by monitoring the induction of key defense-related genes. The efficacy of spraying treatments against peach leaf curl with both inducers was significantly higher compared to the untreated control, showing efficacy in reducing disease severity of up to 62.6% and 73.9% for chitosan and yeast cell wall extracts, respectively. The application of chitosan in combination with copper hydroxide was more efficient in reducing disease incidence and severity, showing efficacy values in the range of 79.5-93.18%. Peach plantlets were also spray-treated with immunity inducers three times prior to leaf inoculation with T. deformans blastospores in their yeast phase. The relative expression levels of nine key defense and priming genes, including those encoding members of pathogenesis-related (PR) proteins and hub genes associated with hormone biosynthesis, were monitored by RT-qPCR across three days after inoculation (dai). The results indicate that pre-treatments with these plant immunity inducers activated the induction of genes involved in salicylic acid (SA) and jasmonate (JA) defense signaling pathways that may offer systemic resistance, coupled with the upregulation of genes conferring direct antimicrobial effects. Our experiments suggest that these two plant immunity inducers could constitute useful components towards the effective control of T. deformans in peach crops.

Probiotics, A New Frontier in Oral Health: Unraveling the Efficacy of Probiotic Metabolites vs. Chlorhexidine on Streptococcus mutans in Dental Plaque

The battle against dental caries has long been fought with conventional antimicrobial agents, with Chlorhexidine leading the charge. However, recent research has delved into the potential of probiotic metabolites as an alternative or adjunctive therapy in the quest for better oral health. In this editorial, we explore the emerging evidence surrounding the efficacy of probiotic metabolites compared to Chlorhexidine, specifically targetting local clinical isolates of Streptococcus mutans within dental plaque. Streptococcus mutans, a key player in the formation of dental plaque, has been a prime target for antimicrobial interventions due to its significant role in tooth decay. Chlorhexidine, a widely used antiseptic, has been a stalwart in dental care. However, its efficacy and potential side effects have prompted researchers to seek alternative approaches. Probiotic metabolites, byproducts of beneficial bacteria, have emerged as a promising avenue, with studies suggesting their ability to promote oral health by modulating the microbial balance.1 Recent studies have begun to unravel the intricate interactions between probiotic metabolites and Streptococcus mutans. These investigations have not only explored the direct antimicrobial effects but also the potential for probiotics to influence the overall microbial environment in the oral cavity. The comparison with Chlorhexidine, a gold standard in dental care, adds depth to our understanding of these alternative therapies.2 The evidence supporting the efficacy of probiotic metabolites in controlling Streptococcus mutans is not only encouraging but also challenges the status quo. A study by Gong SG et al. (2023) demonstrated that probiotic metabolites significantly reduced the growth of Streptococcus mutans in vitro, highlighting their potential as a potent antimicrobial agent.3 This finding is particularly promising given the increasing concerns about antibiotic resistance and the need for sustainable alternatives.
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Topical blood products modulate the effects of ophthalmic antibiotics against common bacterial pathogens in dogs with infectious keratitis.

Bacterial keratitis is a common and serious condition that often leads to vision impairment and potential loss of the eye if not treated promptly and adequately. Topical blood products are often used concurrently with topical antibiotics, helping to mitigate corneal 'melt' from proteases released on the ocular surface. However, blood products are rich in albumin and could affect the efficacy of antibiotics due to drug-protein binding. In this study, serum and plasma samples were harvested from 10 healthy dogs and 10 healthy horses, obtaining fresh and frozen (1 month at -20°C) aliquots for in vitro experiments. Albumin levels were quantified using species-specific ELISA kits. Thirty bacteria (10 Staphylococcus pseudintermedius, 10 Streptococcus canis, 10 Pseudomonas aeruginosa), isolated from canine patients with infectious keratitis, were each tested with blank plates as well as commercial susceptibility plates (Sensititre™ JOEYE2) to assess the minimal inhibitory concentration (MIC) of 17 different antibiotics in the absence (control) or presence of eight test groups: serum or plasma (fresh or frozen) from canines or equines. Albumin concentrations ranged from 13.8-14.6 mg/mL and 25.9-26.5 mg/mL in canine and equine blood products, respectively. A direct antimicrobial effect was observed mostly with equine vs. canine blood products (specifically serum and to a lesser degree plasma), and mostly for Staphylococcus pseudintermedius isolates. MICs generally increased in the presence of blood products (up to 10.8-fold), although MICs also decreased (down to 0.25-fold) for selected antibiotics and ocular pathogens. Median (range) fold changes in MICs were significantly greater (p = 0.004) with the canine blood products [2 (0.67-8.1)] than the equine blood products [2 (0.5-5)]. In practice, clinicians should consider equine over canine blood products (lesser impact on antimicrobial susceptibility), serum over plasma (greater antimicrobial effects), and administering the blood product ≥15 min following the last antibiotic eyedrop to minimize the amount of albumin-antibiotic binding in tear film.

The potential for development of clinically relevant microbial resistance to rifaximin-α: a narrative review.

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. Its important biologic effects are largely at sub-inhibitory concentration. Although in vitro testing of clinical isolates from rifaximin recipients has revealed rifaximin-resistant strains in some studies, the risk of emergent rifaximin-α resistance appears to be lower than for many other antibiotics. Rifaximin-α has been used for many years for traveler's diarrhea with no apparent increase in resistance levels in causative pathogens. Further, rifaximin-α retains its efficacy after long-term and recurrent usage in chronic gastrointestinal disorders. There are numerous reasons why the risk of microbial resistance to rifaximin-α may be lower than that for other agents, including low intestinal bioavailability in the aqueous colon, the mechanisms of action of rifaximin-α not requiring inhibitory concentrations of drug, and the low risk of cross transmission of rifaximin-α resistance between bacterial species. Reported emergence of vancomycin-resistant Enterococcus in liver-disease patients maintained on rifaximin needs to be actively studied. Further studies are required to assess the possible correlation between in vitro resistance and rifaximin-α efficacy.

Direct antimicrobial effects of chemokines on Cryptococcus spp, with special emphasis on a 'CXC' chemokine.

Cryptococcus species are ingenious human pathogens that are widespread globally. They continue to cause over 200,000 deaths per year. Presently due to the rise in resistance and therapy failure, it is necessary to shift the focus to an alternate therapeutic strategy against this pathogen. One promising approach is to emphasize the host defense system in order to develop more precise and customized treatment strategies. In this regard, research has revealed that interferon-γ-inducible CXCL10 chemokine, amongst other chemokines spanning both CXC and CC categories, has a direct killing effect in vitro against Cryptococcus neoformans and Cryptococcus gattii, with a significantly greater microbicidal effect against the former. Moreover, when CXCL10 is used in combination with CCL5, there is a significant reduction in the survival of C. gattii at normal-serum level concentration, indicating a previously unreported synergistic effect of these two chemokines. Confocal and STED microscopic studies have demonstrated that CXCL10 has both cell wall/membrane and intracellular targets against this fungus. These findings present new possibilities for developing chemokine-derived small molecule antifungals and may represent a step forward in creating precision medicine tailored to each patient.

Isolation, Identification and Study of Antimicrobial Property of Potential Probiotic Bacteria from Dairy Products of Lucknow City

Probiotics are the nonpathogenic and alive bacteria that confer good effects on the host. The important property of probiotics is direct antimicrobial effects, stimulation of immunity, competing for adhesion site, completion for nutrients and improvement in digestion. Since ancient times different fermented dairy products have been used as the main source of probiotic bacteria. The main objective of this study was to isolate, identify and characterize lactic acid bacterial strains from different fermented dairy products including yoghurt, cheese, buttermilk and curd. To determine the potentials of probiotics different tests like bile tolerance, salt tolerance, acid tolerance and arginine hydrolysis were performed. In the present study it was observed that all the probiotic isolates were able to grow at low pH (2-6) and they were tolerant against NaCl (2%, 4%, 6%) and bile salt concentration (0.2%, 0.4%, 0.6%). The probiotic isolates were shown to be arginine-positive as on a white background they displayed a bright orange colour. The growths of probiotic cultures were observed at different temperature i.e 10 °C and 45°C and were able to ferment different types of carbohydrates such as glucose, sucrose and lactose. The probiotic isolates showed good antimicrobial activities against the four test organisms. The present study showed that the probiotic strains isolated from different fermented dairy products carry antimicrobial property and can be used to control gut microbiota. The observation of the present study showed that dairy products can be used as a good source of potentially probiotic bacteria.

Application of hypoxia-mesenchymal stem cells in treatment of anaerobic bacterial wound infection: wound healing and infection recovery.

Mesenchymal stromal cells, commonly referred to as MSCs, are a type of multipotent stem cells that are typically extracted from adipose tissue and bone marrow. In the field of tissue engineering and regenerative medicine, MSCs and their exosomes have emerged as revolutionary tools. Researchers are now devoting greater attention to MSCs because of their ability to generate skin cells like fibroblasts and keratinocytes, as well as their distinctive potential to decrease inflammation and emit pro-angiogenic molecules at the site of wounds. More recent investigations revealed that MSCs can exert numerous direct and indirect antimicrobial effects that are immunologically mediated. Collectively, these antimicrobial properties can remove bacterial infections when the MSCs are delivered in a therapeutic setting. Regardless of the positive therapeutic potential of MSCs for a multitude of conditions, transplanted MSC cell retention continues to be a major challenge. Since MSCs are typically administered into naturally hypoxic tissues, understanding the impact of hypoxia on the functioning of MSCs is crucial. Hypoxia has been postulated to be among the factors determining the differentiation of MSCs, resulting in the production of inflammatory cytokines throughout the process of tissue regeneration and wound repair. This has opened new horizons in developing MSC-based systems as a potent therapeutic tool in oxygen-deprived regions, including anaerobic wound infection sites. This review sheds light on the role of hypoxia-MSCs in the treatment of anaerobic bacterial wound infection in terms of both their regenerative and antimicrobial activities.

Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

BackgroundTo improve our understanding of host and intestinal microbiome interaction, this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning piglets. In study 1, piglets received either a high concentration of zinc (Zn) as zinc oxide (ZnO, Zn, 2,690 mg/kg) or a low Zn concentration (100 mg/kg) in the diet during the post weaning period (d 14–23). The effects on the piglet’s small intestinal microbiome and functionality of intestinal tissue were investigated. In study 2, the impact of timing of the dietary zinc intervention was investigated, i.e., between d 0–14 and/or d 14–23 post weaning, and the consecutive effects on the piglet’s intestinal functionality, here referring to microbiota composition and diversity and gene expression profiles.ResultsDifferences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration ZnO content. A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change, where mainly the commensals inter-changed. In the immediate post weaning period, i.e., d 0–14, the highest number of differentially expressed genes (DEGs) in intestinal tissue were observed between animals receiving a diet with a low or high concentration ZnO content, i.e., 23 DEGs in jejunal tissue and 11 DEGs in ileal tissue. These genes are involved in biological processes related to immunity and inflammatory responses. For example, genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration ZnO content compared to low ZnO content in both jejunum and ileum tissue. In the second study, a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration ZnO content compared to low ZnO content.ConclusionsSupplementing a diet with a pharmaceutical level of Zn as ZnO for clinically healthy post weaning piglets influences various aspects intestinal functionality, in particular in the first two weeks post-weaning. The model intervention increased both the alpha diversity of the intestinal microbiome and the expression of a limited number of genes linked to the local immune system in intestinal tissue. The effects do not seem related to a direct antimicrobial effect of ZnO.

Direct and residual antimicrobial effect of 2% chlorhexidine gel, double antibiotic paste and chitosan- chlorhexidine nanoparticles as intracanal medicaments against Enterococcus faecalis and Candida albicans in primary molars: an in-vitro study

BackgroundThorough disinfection of root canals in primary molars may be complicated by the complex root canal morphology. This in-vitro study aimed to compare direct and residual antimicrobial effect of 2% chlorhexidine (CHX) gel, 500 mg/ml double antibiotic paste (DAP) and chitosan-chlorhexidine nanoparticles (CS-CHX NPs) as intracanal medicaments against Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans) in primary molars.MethodsMesial roots of 63 mandibular second primary molars were infected with E. faecalis and C. albicans. Teeth were divided into 9 groups: Ia: (CS-CHX NPs), IIa: (CHX), IIIa: (DAP), IVa: chitosan nanoparticles (CSNPs) in which medicaments were placed for 3 days, groups Ib: (CS-CHX NPs), IIb: CHX, IIIb: (DAP), IVb: (CSNPs) in which medicaments were placed for 7 days, and Group V (control): teeth were infected, irrigated with saline, and sampled 3- and 7-days post-infection. Microbiological samples were obtained after infection, 3, and 7 days after medicament placement and 7 days after medicament removal for both time points. One-way ANOVA, Tukey’s post hoc test and paired t-test were used at p < 0.05.ResultsCS-CHX NPs had the highest anticandidal effect which was comparable to CHX and significantly higher than other medicaments (p < 0.001) at both time points. CS-CHX NPs had the highest effect against E. faecalis which was comparable to DAP and significantly higher than other medicaments (p < 0.001) at 3 days. All medicaments showed similar effect against E. faecalis after 7 days. The 7-days placement significantly increased the antimicrobial effect against both micro-organisms in all groups, except CS-CHX NPs which showed an insignificant increase. CS-CHX NPs showed the highest residual effect against both micro-organisms that increased with 7-days placement.ConclusionCSNPs and CHX combination showed a synergistic effect against both micro-organisms. CS-CHX NPs displayed a higher effect at a shorter period compared to other medicaments, yet its residual effect was higher with 7-days placement.

Perifocal Soft Tissue Reactions in Response to Contaminated Implants With a Composite Antibacterial Coating: Experimental Study

Background. Protection against microbial colonization of surface fixators for metal osteosynthesis can reduce the number of infectious complications.&#x0D; The aim of the study was to experimentally assess early perifocal tissue reactions to metal implants with a composite antibacterial coating under microbial load.&#x0D; Methods. Fragments of steel pins for osteosynthesis (diameter 1 mm) with a four-component antibacterial coating based on polylactide, polyurethane, ciprofloxacin and silver nanoparticles were contaminated by methicillin-resistant S. aureus (MRSA) 43431. They were implanted in rats within the quadriceps femoris. Contaminated uncoated pins were used as a control. The animals were withdrawn from the experiment on the 2nd, 4th, 7th day after implantation. Histopathological specimens from tissue around implants were prepared. A semiquantitative assessment of reactions was performed.&#x0D; Results. The microbial load before implantation was (1.120.26)106 S. aureus cells for the control implants and (0.860.31)106 cells for implants with antibacterial coating. Tissue inflammatory reactions on the second day of implantation were equally evident in the control and investigated groups. There was a significant reduction in the number of immune cells and necrotic detritus, as well as increased growth of connective tissue and neoangiogenesis in the experimental group by the 4th day. The appearance of a less pronounced well-vascularized fibrous capsule around the experimental implants was noted by the 7th day. It indicates a more favorable healing of soft tissues in comparison with the control.&#x0D; Conclusion. Weak morphological manifestations of tissue reactions in response to the fitting of contaminated implants with an antibacterial coating can be associated with both the direct antimicrobial effect of the coating components and the anti-inflammatory activity of silver nanoparticles and ciprofloxacin included in its composition.

Role of Defensins in Tumor Biology.

Defensins have long been considered as merely antimicrobial peptides. Throughout the years, more immune-related functions have been discovered for both the α-defensin and β-defensin subfamily. This review provides insights into the role of defensins in tumor immunity. Since defensins are present and differentially expressed in certain cancer types, researchers started to unravel their role in the tumor microenvironment. The human neutrophil peptides have been demonstrated to be directly oncolytic by permealizing the cell membrane. Further, defensins can inflict DNA damage and induce apoptosis of tumor cells. In the tumor microenvironment, defensins can act as chemoattractants for subsets of immune cells, such as T cells, immature dendritic cells, monocytes and mast cells. Additionally, by activating the targeted leukocytes, defensins generate pro-inflammatory signals. Moreover, immuno-adjuvant effects have been reported in a variety of models. Therefore, the action of defensins reaches beyond their direct antimicrobial effect, i.e., the lysis of microbes invading the mucosal surfaces. By causing an increase in pro-inflammatory signaling events, cell lysis (generating antigens) and attraction and activation of antigen presenting cells, defensins could have a relevant role in activating the adaptive immune system and generating anti-tumor immunity, and could thus contribute to the success of immune therapy.

Oil Cakes of Essential Oil Plants as a Source of Prebiotics for Poultry Production

The oil cakes of essential oil plants were screened for prebiotic properties for further development of prebiotic feeds for livestock animals based on these essential oil plants’ extracts. For screening, a microbiota model of the chicken cecum, which was created on the basis of an artificial intestinal medium, was used. This model renders it possible to simulate conditions close to intestinal ones. Oligofructose, inulin, β-glucan, psyllium seeds, and apple fiber at a concentration of 0.5% were used as substances with known prebiotic properties. The oil cake concentration was 0.5%, 1%, 2%, and 4%. The direct antimicrobial effect of the cakes on intestinal bacteria was also investigated. The ability of the cakes to stimulate a decrease in the pH level by Lactobacillus was studied under conditions close to intestinal ones. It was shown that the cakes of big seed false flax (Camelina sativa), brown mustard (Brassica juncea), and spicate lavender (Lavandula angustifolia) exhibit prebiotic properties in relation to the microbiome of chickens in model experiments. They enhance the acid-forming properties of lactic acid bacteria, thereby lowering the pH of the medium. This leads to a decrease in the number of Enterococcus, Escherichia coli, and lactose-positive bacteria, as well as a complete suppression of Proteus. The optimal oil cake concentrations are 1% and 2%. These oil cakes are promising sources of prebiotics for the development of prebiotic feed for agriculture.

Vertebral Bone Marrow Clot towards the Routine Clinical Scenario in Spine Surgeries: What about the Antimicrobial Properties?

Exploring innovative techniques and treatments to improve spinal fusion procedures is a global challenge. Here, we provide a scientific opinion on the ability of a vertebral bone marrow (vBM) clot to provide a local combined delivery system not only of stem cells, signaling biomolecules and anti-inflammatory factors but also of molecules and proteins endowed with antimicrobial properties. This opinion is based on the evaluation of the intrinsic basic properties of the vBM, that contains mesenchymal stem cells (MSCs), and on the coagulation process that led to the conversion of fibrinogen into fibrin fibers that enmesh cells, plasma but above all platelets, to form the clot. We emphasize that vBM clot, being a powerful source of MSCs and platelets, would allow the release of antimicrobial proteins and molecules, mainly cathelicidin LL- 37, hepcidin, kinocidins and cationic host defense peptides, that are per se gifted with direct and/or indirect antimicrobial effects. We additionally highlight that further studies are needed to deepen this knowledge and to propose vBM clot as multifunctional bioscaffold able to target all the main key challenges for spinal fusion surgery.

Blue Light Therapy in the Management of Chronic Wounds: A Narrative Review of its Physiological Basis and Clinical Evidence

Introduction. Chronic wounds are a significant problem worldwide, with substantial cost to health care systems; thus, a minimally invasive and well-tolerated treatment is attractive. Blue light has shown promise in wound healing through the principle of photobiomodulation. Objective. This review examines the physiological effects of blue light on tissue and the hypothesis that appropriate application of blue light in conjunction with SOC improves wound healing compared with SOC alone. Methods. The authors searched in PubMed, Google Scholar, and the Cochrane Library to identify literature on the mechanism of action of blue light and then examined the clinical evidence. Results. Key physiological pathways of blue light include generation of ROS and nitric oxide, resulting in promotion of angiogenesis, reduced inflammation, and direct antimicrobial effects. These reactions are seen only at low doses; in fact, higher doses may be harmful to tissue. The only primary study with statistical analyses demonstrated wound area reduction of 51% (P =.007) in blue light–irradiated wounds compared with SOC alone. Conclusions. Blue light applied following a strict protocol is safe and shows promise in the management of chronic wounds. The current evidence is poor, however, and randomized trials are required to confirm its clinical utility.

Use and Applicability of Ozone Therapy in Clinical Practice in Dentistry: An Integrative Review

Ozone is a colorless gas with a characteristic odor present in nature in the form of trivalent oxygen. In 2015, the Federal Council of Dentistry (CFO/Brazil) approved the use of ozone therapy and in 2018 the Ministry of Health (MS/Brazil) approved the application of Ozone Therapy as a Complementary Integrative Practice in the Unified Health System. Therefore, the objective of this study was to verify the applicability of ozone therapy in dental practice. This is an integrative literature review whose search was performed in the Medline/Pubmed, LILACS, SciElo, and Google Scholar databases. Studies published in the last 5 years in English, Portuguese or Spanish were eligible. After the search, 312 titles were found and after exclusion of duplicates and analysis of abstracts and full text, 13 articles were included in this review. The literature reports the application of ozone therapy in several areas in the treatment of acute and chronic diseases. As a mechanism of action, ozone has a direct antimicrobial effect, immunoregulation, antioxidant defenses, analgesic, and vasodilator effects. In dentistry, its applicability is mainly in preventive dentistry and as a complement in surgical procedur es, endodontic, and periodontal treatments.

Selection of an Appropriate In Vitro Susceptibility Test for Assessing Anti-Pythium insidiosum Activity of Potassium Iodide, Triamcinolone Acetonide, Dimethyl Sulfoxide, and Ethanol.

The orphan but highly virulent pathogen Pythium insidiosum causes pythiosis in humans and animals. Surgery is a primary treatment aiming to cure but trading off losing affected organs. Antimicrobial drugs show limited efficacy in treating pythiosis. Alternative drugs effective against the pathogen are needed. In-house drug susceptibility tests (i.e., broth dilution, disc diffusion, and radial growth assays) have been established, some of which adapted the standard protocols (i.e., CLSI M38-A2 and CLSI M51) designed for fungi. Hyphal plug, hyphal suspension, and zoospore are inocula commonly used in the drug susceptibility assessment for P. insidiosum. A side-by-side comparison demonstrated that each method had advantages and limitations. Minimum inhibitory and cidal concentrations of a drug varied depending on the selected method. Material availability, user experience, and organism and drug quantities determined which susceptibility assay should be used. We employed the hyphal plug and a combination of broth dilution and radial growth methods to screen and validate the anti-P. insidiosum activities of several previously reported chemicals, including potassium iodide, triamcinolone acetonide, dimethyl sulfoxide, and ethanol, in which data on their anti-P. insidiosum efficacy are limited. We tested each chemical against 29 genetically diverse isolates of P. insidiosum. These chemicals possessed direct antimicrobial effects on the growth of the pathogen in a dose- and time-dependent manner, suggesting their potential application in pythiosis treatment. Future attempts should focus on standardizing these drug susceptibility methods, such as determining susceptibility/resistant breakpoints, so healthcare workers can confidently interpret a result and select an effective drug against P. insidiosum.