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The aim of this work was to provide an overview of available information on the antibacterial and antifungal properties of Epilobium angustifolium extracts. A literature search of Scopus, PubMed/Medline, and Google Scholar for peer-reviewed articles published between January 2000 and June 2023 was undertaken. A total of 23 studies were eligible for inclusion in this review. Significant variation of antimicrobial activity depending on the tested species and strains, type of extract solvent, or plant organs utilized for the extract preparation was found. E. angustifolium extracts were active against both Gram-positive and Gram-negative bacteria and showed antimycotic effects against the fungi of Microsporum canis and Trichophyton tonsurans and the dermatophytes Arthroderma spp. Greater susceptibility of Gram-positive than Gram-negative bacteria to fireweed extracts was found. A strong antibacterial effect was recorded for Staphylococcus aureus, Bacillus cereus, Micrococcus luteus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii including multi-drug resistant strains. E. angustifolium extract might find practical application as an antimicrobial in wound healing, components of cosmetic products for human and animals, or as food preservatives.

The aim of this study is to investigate the effects of herbal supplements administered to goats on sensory quality and volatile flavor compounds in their milk. The experiment was conducted on sixty Polish white improved goats randomly allocated into five feeding groups (four experimental and one control) of twelve goats each. The trial lasted 12 weeks. The experimental animals received supplements containing a mixture of seven or nine different species of herbs at 20 or 40 g/animal/day. The control group received feed without any herbal supplements. Milk obtained from experimental and control groups of animals was characterized by a low content of aroma compounds, with only 11 chemical compounds being identified. Decanoic methyl ester, methylo 2-heptanone and methylo-butanoic methyl ester had the highest share in the total variability of the tested aroma compounds (PCA). During the sensory evaluation, the smell and taste of most of the samples were similar (p > 0.05). However, the addition of herbal feed supplements lowered the concentration of Caproic acid (C6:0), Caprylic acid (C8:0) and Capric acid (C10:0), which caused a significant reduction in the goaty smell of milk. The obtained results indicate that the studied herbal supplements can reduce the intensity of goaty smell and allow goat milk production without modification of other sensory features.

Abstract Critically ill patients with COVID-19 are at increased risk for thrombotic complications which has led to an intense debate surrounding their anticoagulation management. In the absence of data from randomized controlled clinical trials, a number of consensus guidelines and recommendations have been published to facilitate clinical decision-making on this issue. However, substantive differences exist between these guidelines which can be difficult for clinicians. This review briefly summarizes the major societal guidelines and compares their similarities and differences. A common theme in all of the recommendations is to take an individualized approach to patient management and a call for prospective randomized clinical trials to address important anticoagulation issues in this population.

Flax is one of the few plants that are entirely a source of raw materials for further production. Promising directions for the use of flax biomass may be the production of bioenergy in the form of 2G biofuels and the production of “green” composites. The aim of the study is to compare the biomass of fiber flax, linseed and dual-purpose varieties of cultivated flax (Linum usitatissimum L.) susceptibility to the biorefining processes. In the first stage of the research, based on the results of yield structure features and biometric measurements of plants, the most optimal flax line was selected for the fiber flax, linseed and dual purpose. Next, the forms of flax were pretreated with sodium hydroxide (NaOH), the chemical composition was determined and SEM images were taken. The obtaining of bioethanol process SFF (simultaneous saccharification and fermentation) was carried out. In addition, biodegradable polymers were modified with flax biomass, shapes were prepared, and the rheological and mechanical properties, as well as microbiological activity of biocomposites, were determined. The highest concentration of ethanol (8.72 g·L−1) and the greatest susceptibility to mold fungi of the biocomposites were obtained for the fiber flax variety PET 16/20.

BackgroundPostoperative delirium (POD) is an acute altered mental state commonly encountered after cardiac surgery. The pathophysiological mechanisms underlying POD remain unclear. We aimed to identify circulating proteins significantly altered after major cardiac surgery with cardiopulmonary bypass (CPB). We also aimed to enable inferences on associations with POD.MethodsSerum and whole blood samples were collected before CPB (n = 16 patients; n = 8 with POD) and again from the same patients on postoperative day 1. All patients were clinically evaluated for POD on postoperative days 1–3. An aptamer-based proteomics platform (SOMAscan) was used to quantify serum protein abundance in patients with POD compared with non-POD controls. We also performed a lipopolysaccharide (LPS)-based in vitro functional analysis (TruCulture) on whole blood samples from patients with POD and non-POD controls to approximate surgical stress. Cytokine levels were determined using a Luminex immunoassay.ResultsCardiac surgery with CPB resulted in a significant (padj < 0.01) change in 48.8% (637 out of 1,305) of proteins detected by SOMAscan. Gene set enrichment showed that the most impacted biological processes involved myeloid cell activation. Specifically, activation and degranulation of neutrophils were the top five highest-scoring processes. Pathway analyses with the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that metabolic enzymes, particularly those of glycolysis, were elevated in serum concentration after surgery. Several proteins were significantly increased postoperatively in patients diagnosed with POD relative to the non-POD controls, with interleukin-6 (IL-6) showing the greatest fold-change. LPS stimulation of whole blood samples confirmed these findings. Linear regression analysis showed a highly significant correlation between Confusion Assessment Method (CAM) scores and CPB-mediated changes in cGMP-inhibited 3′,5′-cyclic phosphodiesterase A (PDE3A).ConclusionsCardiac surgery with CPB resulted in inflammasome changes accompanied by unexpected increases in metabolic pathways. In exploratory analyses, we found that POD was associated with changes in the expression level of various proteins, most notably IL-6 and PDE3A. This study and ongoing protein biomarker studies will likely help quantify risk or confirm the diagnosis for POD and increase understanding of its pathophysiological mechanisms.

Sixty dairy goats of the Polish white improved breed were randomly assigned to five feeding groups of twelve animals each. The animals received a supplement containing seven herbs at 20 or 40 g/animal/day (experimental groups 1 and 2) and a supplement containing nine herbs at 20 or 40 g/animal/day (experimental groups 3 and 4)m, along with pelleted concentrate feed. Group 5 (the control group) received pelleted feed without any herbal supplements. A significant effect of herbal feed additive on lactic acid bacteria (LAB) count was observed (p < 0.001). The highest number density of LAB was found in the goats receiving the feed additive with nine herbs at 20 g/animal per day (p < 0.05). There was a statistically significant effect of lactation stage on intestinal LAB count (p < 0.001). Regardless of the feeding group, the highest number density of LAB was found in animals at the peak of lactation. The LAB count was also affected by the interaction of diet group × lactation stage (p < 0.0001). A probiotic strain of Lactobacillus fermentum was identified in the faecal samples of goats receiving the herbal additive, but not in the controls. Genetic identification of the microorganisms isolated from the faeces of the experimental goats did not reveal the presence of harmful mould spores, although spores of the fungus Aspergillus fumigatus were detected in the controls.

This study evaluated the effect of adding a new step, termed conditioning, to the traditional processing of leaves from Morus alba var. zolwinska wielkolistna grown in Poland (WML-P). This step, modeled on tea leaves processing, was conducted in a controlled environment on a semi-technical scale. The primary goal was to evaluate the effect of the WML-P conditioning for 1–4 h at 32–35 °C on the content of bioactive compounds (total phenolics, phenolic acids, flavonols, 1-deoxynojirimycin) and antioxidant activity (radical scavenging against DPPH, antioxidant capacity, chelating activity and ferric reducing antioxidant potential) of the lyophilized extracts. For the first time WML-P extracts content was comprehensively characterized by assessing dietary fiber fractions, fatty acids, amino acids, macro- and microelements and chlorophyll content. Compared to the traditional process, adding the conditioning step to WML-P processing resulted in an increased total phenolics content, radical scavenging capacity, ability to quench 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and iron-chelating ability in the lyophilized extracts. The beneficial effect depended on conditioning time. The highest flavonols and phenolic acids content were found after 2-h conditioning. We concluded that adding a 2-h conditioning step to traditional WML-P processing results in getting WML-P lyophilized extract with increased bioactive compounds content and high antioxidant activity.

Developing new adjuvants/vaccines and better understanding their mode-of-action is an important task. To specifically improve birch pollen allergy treatment, we designed a fusion protein consisting of major birch pollen allergen Betv1 conjugated to the TLR5-ligand flagellin (rFlaA:Betv1). This study investigates the immune-modulatory effects of rFlaA:Betv1 on airway epithelial cells. LA-4 mouse lung epithelial cells were stimulated with rFlaA:Betv1 in the presence/absence of various inhibitors with cytokine- and chemokine secretion quantified by ELISA and activation of intracellular signaling cascades demonstrated by Western blot (WB). Either LA-4 cells or LA-4-derived supernatants were co-cultured with BALB/c bone marrow-derived myeloid dendritic cells (mDCs). Compared to equimolar amounts of flagellin and Betv1 provided as a mixture, rFlaA:Betv1 induced higher secretion of IL-6 and the chemokines CCL2 and CCL20 from LA-4 cells and a pronounced MAPK- and NFκB-activation. Mechanistically, rFlaA:Betv1 was taken up more strongly and the induced cytokine production was inhibited by NFκB-inhibitors, while ERK- and p38-MAPK-inhibitors only suppressed IL-6 and CCL2 secretion. In co-cultures of LA-4 cells with mDCs, rFlaA:Betv1-stimulated LA-4 cells p38-MAPK- and COX2-dependently secreted PGE2, which modulated DC responses by suppressing pro-inflammatory IL-12 and TNF-α secretion. Taken together, these results contribute to our understanding of the mechanisms underlying the strong immune-modulatory effects of flagellin-containing fusion proteins.

ABSTRACT: The white mulberry leaves are typically available on the market in dried or encapsulated form. It was assumed in the study that appropriate drying of leaves of the white mulberry is significant for obtaining intermediate products with high content of compounds having anti-oxidative activity. The purpose of the study was to determine the influence of the temperature of mulberry leaves air drying on the content of phenolic acids and flavonols. It has been determined that the content of these compounds in the leaves depended on the drying temperature. Drying at 60 °C favored release of phenolic acids and flavonols from complexes and/or formation of new compounds. Their total content was 22% higher than in leaves dried at 30 °C. Drying at 90 °C reduced the phenolic acid and flavonol content by 24%. The most favorable drying temperature was 60 °C.

Macrophage receptor with collagenous structure (MARCO) contributes to fungal containment during the early/innate phase of cryptococcal infection; however, its role in adaptive antifungal immunity remains unknown. Using a murine model of cryptococcosis, we compared host adaptive immune responses in wild-type and MARCO−/− mice throughout an extended time course post-infection. Unlike in early infection, MARCO deficiency resulted in improved pulmonary fungal clearance and diminished cryptococcal dissemination during the efferent phase. Improved fungal control in the absence of MARCO expression was associated with enhanced hallmarks of protective Th1-immunity, including higher frequency of pulmonary TNF-α-producing T cells, increased cryptococcal-antigen-triggered IFN-γ and TNF-α production by splenocytes, and enhanced expression of M1 polarization genes by pulmonary macrophages. Concurrently, we found lower frequencies of IL-5- and IL-13-producing T cells in the lungs, impaired production of IL-4 and IL-10 by cryptococcal antigen-pulsed splenocytes, and diminished serum IgE, which were hallmarks of profoundly suppressed efferent Th2 responses in MARCO-deficient mice compared to WT mice. Mechanistically, we found that MARCO expression facilitated early accumulation and alternative activation of CD11b+ conventional DC (cDC) in the lung-associated lymph nodes (LALNs), which contributed to the progressive shift of the immune response from Th1 toward Th2 at the priming site (LALNs) and local infection site (lungs) during the efferent phase of cryptococcal infection. Taken together, our study shows that MARCO can be exploited by the fungal pathogen to promote accumulation and alternative activation of CD11b+ cDC in the LALN, which in turn alters Th1/Th2 balance to promote fungal persistence and dissemination.

This study evaluated the antioxidant activity and anti-diabetic effect of mulberry (Morus alba L. wielkolistna zolwinska) leaf extracts in diabetic rats fed a high-fat diet. After initial 4-week high-fat diet, streptozotocin was injected in Wistar rats to induce non-obese type 2 diabetes. After confirmation of diabetes, animals were treated with mulberry dried leaves, leaf-derived ethanol or acetone extracts added to high-fat diet for 4 weeks. Mulberry ethanol extract with higher level of phenolics – chlorogenic acid and flavonol glucosides was more effective than acetone extract or dry leaves in the lowering of blood glucose, increasing insulin level and markers of antioxidant activity. The results confirm key mechanisms related to the effect of mulberry and its bioactive components on modulation of glucose metabolism through correcting hyperglycaemia, increasing insulin secretion, and improving antioxidant status in STZ-induced non-obese diabetic rat model. Antidiabetic effects exerted by mulberry leaves might depend on the extraction process.

Flax is one of the few plants that are entirely a source of raw materials for further production. Promising directions for the use of flax biomass may be the production of bioenergy in the form of 2G biofuels and the production of "green" composites. The aim of the study is to compare the biomass of fiber flax, linseed and dual-purpose varieties of cultivated flax (Linum usitatissimum L.) susceptibility to the biorefining processes. In the first stage of the research, based on the results of yield structure features and biometric measurements of plants, the most optimal flax line was selected for the fiber flax, linseed and dual purpose. Next, the forms of flax were pretreated with sodium hydroxide (NaOH), the chemical composition was determined and SEM images were taken. The obtaining of bioethanol process SFF (simultaneous saccharification and fermentation) was carried out. In addition, biodegradable polymers were modified with flax biomass, shapes were prepared, and the rheological and mechanical properties, as well as microbiological activity of biocomposites, were determined. The highest concentration of ethanol (8.72 g·L−1) and the greatest susceptibility to mold fungi of the biocomposites were obtained for the fiber flax variety PET 16/20. [ABSTRACT FROM AUTHOR]

Background. TLR ligands can promote Th1-biased immune responses, mimicking potent stimuli of viruses and bacteria. Aim. To investigate the adjuvant properties of dual TLR2/7 ligands compared to those of the mixture of both single ligands. Methods. Dual TLR2/7 ligands: CL401, CL413, and CL531, including CL264 (TLR7-ligand) and Pam2CysK4 (TLR2-ligand), were used. Immune-modulatory capacity of the dual ligands with the individual ligands alone or as a mixture in mouse BMmDCs, BMmDC:TC cocultures, or BMCMCs was compared and assessed in naïve mice and in a mouse model of OVA-induced intestinal allergy. Results. CL413 and CL531 induced BMmDC-derived IL-10 secretion, suppressed rOVA-induced IL-5 secretion from OVA-specific DO11.10 CD4+ TCs, and induced proinflammatory cytokine secretion in vivo. In contrast, CL401 induced considerably less IL-10 secretion and led to IL-17A production in BMmDC:TC cocultures, but not BMCMC IL-6 secretion, or IL-6 or TNF-α production in vivo. No immune-modulating effects were observed with single ligands. All dual TLR2/7 ligands suppressed DNP-induced IgE-and-Ag-specific mast cell degranulation. Compared to vaccination with OVA, vaccination with the mixture CL531 and OVA, significantly suppressed OVA-specific IgE production in the intestinal allergy model. Conclusions. Based on beneficial immune-modulating properties, CL413 and CL531 may have utility as potential adjuvants for allergy treatment.

ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. IMPORTANCE Increased susceptibility to invasive fungal infections in patients on anti-TNF-α therapies underlines the need for understanding the cellular effects of TNF-α signaling in promoting protective immunity to fungal pathogens. Here, we demonstrate that early TNF-α signaling is required for classical activation and accumulation of DC in LALN of C. neoformans-infected mice. Subsequent transcriptional initiation of Th17 followed by Th1 programming in LALN results in pulmonary accumulation of gamma interferon- and interleukin-17A-producing T cells and effective fungal clearance. All of these crucial steps are severely impaired in mice that undergo anti-TNF-α treatment, consistent with their inability to clear C. neoformans. This study identified critical interactions between cells of the innate immune system (DC), the emerging T cell responses, and cytokine networks with a central role for TNF-α which orchestrate the development of the immune protection against cryptococcal infection. This information will be important in aiding development and understanding the potential side effects of immunotherapies.

Background. The detoxified TLR4-ligand Monophosphoryl Lipid A (MPLA) is the first approved TLR-agonist used as adjuvant in licensed vaccines but has not yet been explored as part of conjugated vaccines. Objective. To investigate the immune-modulating properties of a fusion protein consisting of MPLA and Ovalbumin (MPLA : Ova). Results. MPLA and Ova were chemically coupled by stable carbamate linkage. MPLA : Ova was highly pure without detectable product-related impurities by either noncoupled MPLA or Ova. Light scattering analysis revealed MPLA : Ova to be aggregated. Stimulation of mDC and mDC : DO11.10 CD4+ TC cocultures showed a stronger activation of both mDC and Ova-specific DO11.10 CD4+ TC by MPLA : Ova compared to the mixture of both components. MPLA : Ova induced both strong proinflammatory (IL-1β, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokine responses from mDCs while also boosting allergen-specific Th1, Th2, and Th17 cytokine secretion. Conclusion. Conjugation of MPLA and antigen enhanced the immune response compared to the mixture of both components. Due to the nonbiased boost of Ova-specific Th2 and Th17 responses while also inducing Th1 responses, this fusion protein may not be a suitable vaccine candidate for allergy treatment but may hold potential for the treatment of other diseases that require a strong stimulation of the host’s immune system (e.g., cancer).

Enzymic hydrolysates were obtained from cracklings (CEH and CEH*) using alcalase. Acid hydrolysates were prepared from cracklings (CAH) and chicken feathers (FAH). The degree of hydrolysis (DH) of CEH and CEH* were 14 and 15.1%, respectively. CAH, its Sephadex G-25 fraction (CAH*) and FAH were characterised by DH of 53.8%, 47.8% and 46.2%. The electrophoreograms of enzymic hydrolysates were characterised by one high and sharp peak and several not base line separated peaks. More single and sharp peaks were observed on the electrophoreograms of acid hydrolysates. Migration times of the majority of peptides present in enzymic hydrolysates ranged between 4 and 6 min.