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Lactococcus lactis T-21 is a lactic acid bacterium isolated from wild cranberries in Japan that demonstrates significant immunomodulatory properties and has been incorporated into commercial health products. However, probiogenomic analyses specific to T-21 have remained largely unexplored. This study performed a thorough genomic characterisation of T-21 and evaluated its safety in initial clinical trials. Genomic analysis revealed substantial genetic diversity and metabolic capabilities, including enhanced fermentative potential demonstrated by its ability to metabolise a wide range of plant-derived carbohydrates, and genetic determinants associated with exopolysaccharide biosynthesis and nisin production, distinguishing T-21 from domesticated dairy strains. These attributes, reflective of its wild plant origin, may contribute to its metabolic versatility and unique probiotic functionalities. A preliminary clinical trial assessing the safety of T-21-fermented milk in healthy Japanese adults indicated no significant adverse outcomes, corroborating its safety for human consumption. Together, these findings support the feasibility of utilising non-dairy, wild plant-origin strains in dairy fermentation processes as probiotics. This study expands our understanding of the genomic basis for T-21's probiotic potential and lays the groundwork for further investigations into its functional mechanisms and potential applications in promoting human health. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to evaluate the wound healing potential of Eurasian propolis by analyzing the phytochemical profile and the biological effects of three representative propolis samples. Methods: Specific colorimetric assays were used to estimate the total phenolic and flavonoid contents and the triterpenoids content. Some of the main components of Eurasian propolis (pinocembrin, pinobanksin, CAPE, chrysin and galangin) were analyzed using HPLC-DAD. Scavenging activity and total antioxidant capacity were assessed through DPPH and ORAC assays, respectively. Human keratinocyte, fibroblast, and monocytic cell lines were used for the biological in vitro analyses. The direct wound healing properties were tested through scratching assays and ELISA kits for the assessment of the production of growth factors (FGF-7, Latency Associated Peptide-LAP), while the indirect effects were evaluated through the estimation of the levels of MMP9, IL-1β, IL-8, and TNF-α using ELISA kits together with a cell-free test on the inhibition capacity on collagenases. Network Pharmacology analysis was employed to further explore possible mechanisms of the action of propolis on the healing process. Results: The analyses confirmed the high phenolic content of Eurasian propolis (142.50–211.30 mg GAE/g), dominated by flavonoids (95.50–196.80 mg Galangin Equivalents/g), and terpenes (431.50–650.00 mg β-sitosterol Equivalents/g), while also verifying the significant antioxidant (4.9–8.9 mM/g Trolox Equivalents) and antiradical (DPPH IC50 26.1–54.4 μg/mL) activities. The samples showed indirect wound healing properties by mitigating inflammation and remodeling (reduced IL-1β and MMP9) and potentially modulating the immune response (upregulated IL-8). In vitro studies confirmed these effects, demonstrating decreased MMP9 production and collagenase inhibition when cells were co-treated with propolis and a stressor. Propolis also suppressed IL-1β release in fibroblasts, although its impact on TNF-α was inconclusive. Notably, co-treatment upregulated IL-8 in monocytes, suggesting a potential immunomodulatory role. Conclusions: Eurasian propolis may not directly stimulate cell proliferation during wound healing. Its anti-inflammatory and immunomodulatory properties could indicate an indirect contribution in helping the process. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, leading to significant disability through neurodegeneration. Despite advances in the understanding of MS pathophysiology, effective treatments remain limited. Mesenchymal stem cells (MSCs) have gained attention as a potential therapeutic option due to their immunomodulatory and regenerative properties. This review examines MS pathogenesis, emphasizing the role of immune cells, particularly T cells, in disease progression, and explores MSCs' therapeutic potential. Although preclinical studies in animal models show MSC efficacy, challenges such as donor variability, culture conditions, migratory capacity, and immunological compatibility hinder widespread clinical adoption. Strategies like genetic modification, optimized delivery methods, and advanced manufacturing are critical to overcoming these obstacles. Further research is needed to validate MSCs' clinical application in MS therapy. [ABSTRACT FROM AUTHOR]

Lactococcus lactis T-21 is a lactic acid bacterium isolated from wild cranberries in Japan that demonstrates significant immunomodulatory properties and has been incorporated into commercial health products. However, probiogenomic analyses specific to T-21 have remained largely unexplored. This study performed a thorough genomic characterisation of T-21 and evaluated its safety in initial clinical trials. Genomic analysis revealed substantial genetic diversity and metabolic capabilities, including enhanced fermentative potential demonstrated by its ability to metabolise a wide range of plant-derived carbohydrates, and genetic determinants associated with exopolysaccharide biosynthesis and nisin production, distinguishing T-21 from domesticated dairy strains. These attributes, reflective of its wild plant origin, may contribute to its metabolic versatility and unique probiotic functionalities. A preliminary clinical trial assessing the safety of T-21-fermented milk in healthy Japanese adults indicated no significant adverse outcomes, corroborating its safety for human consumption. Together, these findings support the feasibility of utilising non-dairy, wild plant-origin strains in dairy fermentation processes as probiotics. This study expands our understanding of the genomic basis for T-21’s probiotic potential and lays the groundwork for further investigations into its functional mechanisms and potential applications in promoting human health.

Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota‐derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota‐derived metabolites, such as short‐chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine‐N‐oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined. [ABSTRACT FROM AUTHOR]

The emergence of infectious diseases, including viral zoonoses, has allowed intensive research into novel therapeutic approaches. Stem cell therapy, mostly using mesenchymal stem cells (MSCs), has garnered significant attention due to the immunomodulatory properties and tissue repair capabilities. MSCs have demonstrated promise in treating severe COVID-19 cases and several clinical trials have revealed that MSC therapy improves 28-day survival rates, reduces mortality, and accelerates recovery. These cells effectively mitigate a cytokine storm, relieve pulmonary symptoms, and positively influence organ recovery, including the liver and kidneys. Bioanalytical readings return to normal following MSC administration, emphasizing the potential in managing COVID-19-induced complications. MSC therapy offers a potential solution for infection with the influenza virus, which is responsible for historical pandemics and epidemics, and remains a global health concern. MSCs inhibit immune cell-mediated responses and reduce lung damage in animal models, and despite antiviral drugs, influenza-induced manifestations persist. MSCs, with an ability to counteract inflammation and promote lung tissue repair, hold promise for managing influenza infections. While MSCs offer therapeutic benefits, certain challenges remain. Specifically, ethical considerations, regulatory hurdles, and scalability are some of the challenges that hinder widespread adoption. However, ongoing systematic reviews and meta-analyses provide real-time insight that support the security and effectiveness of MSC therapy.

Spiramycin is a natural 16-membered macrolide antibiotic that has been used in clinical practice for about 70 years. Despite long-term use, spiramycin retains its position in clinical practice; the resistance of the main respiratory and urogenital pathogens is lower to spiramycin than to 14- and 15-membered macrolides. The interest in spiramycin is due to the fact that its physico-chemical and pharmacokinetic properties are similar to the last semi-synthetic macrolides, and it lacks the disadvantages of erythromycin. Special biological properties of spiramycin explain its consistently high clinical efficacy that has lasted for 70 years of clinical use in various infections. It is necessary to emphasize the uniqueness of spiramycin as an antibiotic with not only the direct effect on microbes, but also non-antibiotic properties. This allowed the experts at the time to declare the «paradox» of spiramycin — the presence of a higher real clinical efficacy than expected according to in vitro studies. Such properties of spiramycin include pro-antibiotic and post-antibiotic effects, immunomodulatory effect, as well as high intracellular and extracellular concentrations of the antibiotic. The review discusses antimicrobial, pharmacokinetic, and pharmacodynamic characteristics of spiramycin and its place in the treatment of various infections — respiratory, ENT, urogenital, gynecological, and dental.

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Holothurians (or sea cucumbers) are echinoderms and are found in all areas of the world oceans. These animals produce special low-molecular metabolites - triterpene glycosides, which are a means of chemical protection of holothurians from predators. The content of triterpene glycosides in the tissues of holothurians can reach a significant amount of up to 1 g/kg, and especially many of these compounds are localized in the Cuvierian tubules - special protection organ presents in a number of tropical holothurians. Tritirepene glycosides of holothurians are quite toxic, they exhibit hemolytic, cytotoxic and neurotoxic activity at a concentration range of 1×104–1×106 M. The toxic properties of glycosides are based on the ability of these compounds to interact with ∆5-sterols (mainly cholesterol) of plasma membranes and form ion-conducting complexes. In turn, this leads to a change in the ion permeability and selectivity of biomembranes, disruption of barrier properties, ion homeostasis and osmolarity of cells, and further to cell lysis and death.Contact with holoturias when diving in shallow water, which is fraught with damage to the eyes and mucous membranes by triterpene glycosides, may be of some danger to humans. Excessive consumption of commercial edible holothurians in food, especially without prior heat treatment, as is customary in some South-East Asia countries, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death.The holothurians are animals commercially harvested in Russia. They are used in food and for the preparation of medicinal supplements and preparations. Excessive consumption of commercial edible holothurians for food, especially without long-term boiling, as is customary in Southeast Asia, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death. The use of dietary supplements with an uncontrolled glycoside content is fraught with similar consequences, and the presence of immunosuppressants among glycosides that have fallen into such additives and drugs can worsen the condition of patients or sick animals. Control of the qualitative and quantitative content of glycosides in food and medicinal products from holothurians should be an integral part of measures to improve the biological safety of citizens of the Russian Federation.

This study investigates the effects of Temporin-Rb, an antimicrobial peptide, on A549 cells’ viability and pro-inflammatory gene expression. The MTT assay revealed a dose- and time-dependent reduction in cell viability. RT-PCR analysis demonstrated significant changes in the expression levels of pro-inflammatory cytokines, with transforming growth factor-beta (TGFβ) exhibiting the most pronounced alterations (15- fold), implicating its role in mediating the peptide’s effects. The study highlights the potential of selectively targeting specific pro-inflammatory signaling pathways, like TGFβ, to modulate immune responses effectively. The differential effects of Temporin-Rb on pro-inflammatory cytokine expression were further analyzed, with TGFβ and interleukin-1 (IL-1β) showing substantial alterations. ELISA confirmed Temporin-Rb’s ability to modulate TGFβ production by A549 cells, supporting its immunomodulatory properties. These findings contribute to the understanding of Temporin-Rb’s therapeutic potential as an antimicrobial and immunomodulatory agent in various cellular models. Further research is warranted to explore its underlying mechanisms and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal/stem cells (MSCs) are the most promising stem cells for the treatment of multiple inflammatory and immune diseases due to their easy acquisition and potent immuno-regulatory capacities. These immune functions mainly depend on the MSC secretion of soluble factors. Recent studies have shown that the metabolism of MSCs plays critical roles in immunomodulation, which not only provides energy and building blocks for macromolecule synthesis but is also involved in the signaling pathway regulation. Aim of Review: A thorough understanding of metabolic regulation in MSC immunomodulatory properties can provide new sights to the enhancement of MSC-based therapy. Key scientific Concepts of Review: MSC immune regulation can be affected by cellular metabolism (glucose, adenosine triphosphate, lipid and amino acid metabolism), which further mediates MSC therapy efficiency in inflammatory and immune diseases. The enhancement of glycolysis of MSCs, such as signaling molecule activation, inflammatory cytokines priming, or environmental control can promote MSC immune functions and therapeutic potential. Besides glucose metabolism, inflammatory stimuli also alter the lipid molecular profile of MSCs, but the direct link with immunomodulatory properties remains to be further explored. Arginine metabolism, glutamine-glutamate metabolism and tryptophan-kynurenine via indoleamine 2,3-dioxygenase (IDO) metabolism all contribute to the immune regulation of MSCs. In addition to the metabolism dictating the MSC immune functions, MSCs also influence the metabolism of immune cells and thus determine their behaviors. However, more direct evidence of the metabolism in MSC immune abilities as well as the underlying mechanism requires to be uncovered.

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of Au nanoparticles by Mentha piperita as a natural reducing and stabilising agent in alkaline medium without using any toxic reducing agent. The biosynthesized Au NPs@Mentha piperita were characterised by advanced physicochemical techniques like ultraviolet-visible (UV-Vis), Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX), and X-ray Diffraction (XRD) study. It has been established that Au NPs@Mentha piperita have a spherical shape with a mean diameter from ∼10 nm. To survey the cytotoxicity effects of Au NPs@Mentha piperita, MTT assay was used on HUVEC cell line. To survey the antioxidant properties of Au NPs@Mentha piperita, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The Au NPs@Mentha piperita inhibited half of the DPPH molecules in the concentration of 113 µg/mL. In the in vivo, wistar rats were divided to four groups; non-sensitised, sensitised to ovalbumin, sensitised and treated with dexamethasone (1.25 μg/mL), and Au NPs@Mentha piperita (5 μg/mL) in drinking water for 21 days. The levels of total protein (TP), phospholipase A2 (PLA2), immunoglobulin E (IgE), IFN-γ/IL-4 ratio, interferon gamma (IFN-γ), and interleukin 4 (IL-4) in BALF, and lung pathological changes were examined. A significant increase in PLA2, IgE, IL-4, and TP levels, all lung pathological indices as well as significant decrease in IFN-γ/IL-4 ratio was seen in the asthmatic compared to the control rats. Treatment with Au NPs@Mentha piperita (5 μg/mL) resulted in decreased PLA2, IgE, IL-4, and TP levels, but increased IFN-γ/IL-4 ratio compared to untreated sensitised rats. The Au NPs@Mentha piperita significantly improved the pathological changes of sensitised rats. The improvement effects of higher concentrations of the Au NPs@Mentha piperita extract were significantly more than those of dexamethasone. The improvement effects of Au NPs@Mentha piperita on pathological changes, immunological and inflammatory markers in sensitised rats comparable or even more potent than dexamethasone suggests the therapeutic potential of the nanoparticle in asthma. After confirming these results in clinical trial studies, Au NPs@Mentha piperita can be used as a new drug for the treatment of asthma in humans.

Immune system modulation is an intriguing part of scientific research. It is well established that the immune system plays a crucial role in orchestrating cellular and molecular key mediators, thus establishing a powerful defense barrier against infectious pathogens. Gut microbiota represent a complex community of approximately a hundred trillion microorganisms that live in the mammalian gastrointestinal (GI) tract, contributing to the maintenance of gut homeostasis via regulation of the innate and adaptive immune responses. However, impairment in the crosstalk between intestinal immunity and gut microbiota may reflect on detrimental health issues. In this context, many studies have indicated that probiotics and their bioactive compounds, such as bacteriocins and short chain fatty acids (SCFAs), display distinct immunomodulatory properties through which they suppress inflammation and enhance the restoration of microbial diversity in pathological states. This review highlights the fundamental features of probiotics, bacteriocins, and SCFAs, which make them ideal therapeutic agents for the amelioration of inflammatory and autoimmune diseases. It also describes their underlying mechanisms on gut microbiota modulation and emphasizes how they influence the function of immune cells involved in regulating gut homeostasis. Finally, it discusses the future perspectives and challenges of their administration to individuals. [ABSTRACT FROM AUTHOR]

Abstract Background Despite promising results in clinical studies, the mechanism for the beneficial effects of allogenic cell-based therapies remains unclear. Macrophages are not only critical mediators of inflammation but also critical players in cardiac remodeling. We hypothesized that transplanted allogenic rat cardiac progenitor cells (rCPCs) augment T-regulatory cells which ultimately promote proliferation of M2 like macrophages by an as-yet undefined mechanism. Methods and results To test this hypothesis, we used crossover rat strains for exploring the mechanism of myocardial repair by allogenic CPCs. Human CPCs (hCPCs) were isolated from adult patients undergoing coronary artery bypass grafting, and rat CPCs (rCPCs) were isolated from male Wistar-Kyoto (WKY) rat hearts. Allogenic rCPCs suppressed the proliferation of T-cells observed in mixed lymphocyte reactions in vitro. Transplanted syngeneic or allogeneic rCPCs significantly increased cardiac function in a rat myocardial infarct (MI) model, whereas xenogeneic CPCs did not. Allogeneic rCPCs stimulated immunomodulatory responses by specifically increasing T-regulatory cells and M2 polarization, while maintaining their cardiac recovery potential and safety profile. Mechanistically, we confirmed the inactivation of NF-kB in Treg cells and increased M2 macrophages in the myocardium after MI by transplanted CPCs derived GDF15 and it’s uptake by CD48 receptor on immune cells. Conclusion Collectively, these findings strongly support the active immunomodulatory properties and robust therapeutic potential of allogenic CPCs in post-MI cardiac dysfunction.

[Display omitted] • Metabolism plays critical roles in the MSCs immunomodulatory properties. • Manipulation the metabolism in MSCs can enhance their therapeutic effects. • MSCs can affect the immune cells metabolism and determine their behaviors. • The more direct evidence of MSCs immunometabolism is needed to be uncovered. • The mechanism of metabolism influencing immunomodulatory properties in MSCs is unclear. Mesenchymal stromal/stem cells (MSCs) are the most promising stem cells for the treatment of multiple inflammatory and immune diseases due to their easy acquisition and potent immuno-regulatory capacities. These immune functions mainly depend on the MSC secretion of soluble factors. Recent studies have shown that the metabolism of MSCs plays critical roles in immunomodulation, which not only provides energy and building blocks for macromolecule synthesis but is also involved in the signaling pathway regulation. A thorough understanding of metabolic regulation in MSC immunomodulatory properties can provide new sights to the enhancement of MSC-based therapy. MSC immune regulation can be affected by cellular metabolism (glucose, adenosine triphosphate, lipid and amino acid metabolism), which further mediates MSC therapy efficiency in inflammatory and immune diseases. The enhancement of glycolysis of MSCs, such as signaling molecule activation, inflammatory cytokines priming, or environmental control can promote MSC immune functions and therapeutic potential. Besides glucose metabolism, inflammatory stimuli also alter the lipid molecular profile of MSCs, but the direct link with immunomodulatory properties remains to be further explored. Arginine metabolism, glutamine-glutamate metabolism and tryptophan-kynurenine via indoleamine 2,3-dioxygenase (IDO) metabolism all contribute to the immune regulation of MSCs. In addition to the metabolism dictating the MSC immune functions, MSCs also influence the metabolism of immune cells and thus determine their behaviors. However, more direct evidence of the metabolism in MSC immune abilities as well as the underlying mechanism requires to be uncovered. [ABSTRACT FROM AUTHOR]

The ability of MSCs to modulate the inflammatory environment is well recognized, but understanding the molecular mechanisms responsible for these properties is still far from complete. Prostaglandin E2 (PGE2), a product of the cyclooxygenase 2 (COX-2) pathway, is indicated as one of the key mediators in the immunomodulatory effect of MSCs. Due to the pleiotropic effect of this molecule, determining its role in particular intercellular interactions and aspects of cell functioning is very difficult. In this article, the authors attempt to summarize the previous observations regarding the role of PGE2 and COX-2 in the immunomodulatory properties and other vital functions of MSCs. So far, the most consistent results relate to the inhibitory effect of MSC-derived PGE2 on the early maturation of dendritic cells, suppressive effect on the proliferation of activated lymphocytes, and stimulatory effect on the differentiation of macrophages into M2 phenotype. Additionally, COX-2/PGE2 plays an important role in maintaining the basic life functions of MSCs, such as the ability to proliferate, migrate and differentiate, and it also positively affects the formation of niches that are conducive to both hematopoiesis and carcinogenesis. [ABSTRACT FROM AUTHOR]

Nowadays it is observed that the number of stem-cell based experimental therapies in neurodegenerative disorders is massively increasing. Most of the clinical trials registered to date have been based on autologous mesenchymal stem/stromal cells (MSC) obtained from somatic tissues. In the conducted clinical trials neither serious side effects, nor statistically significant improvement were observed. The lack of statistical significance could result from a relatively small number of patients involved in clinical trials or highly incoherent study protocols. However, most clinical groups describe a trend towards improvement in MSC-treated patients. Hence, the question arises which factors associated with MSC-based therapy may be the key and result in better therapeutic response. In the presented paper, we summarize, in our opinion, the most important factors that could increase the effectiveness of this therapy.

Water-soluble polypeptides from pilose antler (PAWPs) are a traditional Chinese functional food and have been reported to inhibit triple-negative breast cancer (TNBC) in mice. Thus, in this study, we characterized PAWPs through peptidomics, and 405 total polypeptides were finally identified. Subsequently, our results indicate that PAWPs combined with neoadjuvant chemotherapy (NAC) result in a markedly lower spleen index compared with that in other groups. Next, 25 subpopulations of T cells were identified by multi-parametric flow cytometry in the lungs, spleen, and peripheral blood of different groups. These results indicated that PAWPs combined with NAC promote the proliferation of CD3+ T cells in the spleen and significantly affect the fate of the T-cell subpopulation. Moreover, PAWPs combined with NAC increased the infiltration of CD4+ interferon-γ+ T cells into tumor tissues. Our results showed that PAWPs have immunoregulatory functions and chemosensitizing effects, with good prospects for future clinical application. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the impact of a wild strain of Lactobacillus plantarum (PL4) on the production of IL-10 and T helper (Th) 17 related cytokines, including interleukin (IL)-17A, IL-17F, IL-21, and IL-22, compared to a standard probiotic strain, Lactobacillus plantarum. PL4 was isolated from Lighvan cheese and its probiotic potential was proved before. Probiotics with immune regulatory activity might be effective in the case of Th17 cells and IL-17-related pathways, which are involved in the pathogenesis and are associated with a worse result of some diseases. These regulatory effects might be arising from different bacterial cell substances. Materials and Methods: Peripheral blood mononuclear cells (PBMC) were treated with cell debris and cell extract of both strains with and without human anti-CD3/CD28 T-cell activator beads in order to determine immunomodulatory effects of the strains. A number of cytokines were assessed. Results: Bacterial cell debris and extract had no stimulatory or suppressive effects on the Th17 related cytokines and only the debris of both strains increased IL-10 production significantly. When PBMC pretreated with bacterial cell debris or extracts was stimulated with anti-CD3/CD28 beads, both strains down-regulated IL-17F. PL4 extract could decrease IL-21 and IL-17A but conversely, its debris increased these cytokines. Conclusion: Pretreatment with PL4 extract induced lower levels of IL-17A, IL-17F, IL-21 and IL-10 in stimulated PBMCs, implying an antiinflammatory potential of this strain. Significant differences among the effects of the strains confirmed strain dependency of their immunomodulatory properties. [ABSTRACT FROM AUTHOR]

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of Au nanoparticles by Mentha piperita as a natural reducing and stabilising agent in alkaline medium without using any toxic reducing agent. The biosynthesized Au NPs@Mentha piperita were characterised by advanced physicochemical techniques like ultraviolet-visible (UV-Vis), Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX), and X-ray Diffraction (XRD) study. It has been established that Au NPs@Mentha piperita have a spherical shape with a mean diameter from ∼10 nm. To survey the cytotoxicity effects of Au NPs@Mentha piperita, MTT assay was used on HUVEC cell line. To survey the antioxidant properties of Au NPs@Mentha piperita, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The Au NPs@Mentha piperita inhibited half of the DPPH molecules in the concentration of 113 µg/mL. In the in vivo, wistar rats were divided to four groups; non-sensitised, sensitised to ovalbumin, sensitised and treated with dexamethasone (1.25 μg/mL), and Au NPs@Mentha piperita (5 μg/mL) in drinking water for 21 days. The levels of total protein (TP), phospholipase A2 (PLA2), immunoglobulin E (IgE), IFN-γ/IL-4 ratio, interferon gamma (IFN-γ), and interleukin 4 (IL-4) in BALF, and lung pathological changes were examined. A significant increase in PLA2, IgE, IL-4, and TP levels, all lung pathological indices as well as significant decrease in IFN-γ/IL-4 ratio was seen in the asthmatic compared to the control rats. Treatment with Au NPs@Mentha piperita (5 μg/mL) resulted in decreased PLA2, IgE, IL-4, and TP levels, but increased IFN-γ/IL-4 ratio compared to untreated sensitised rats. The Au NPs@Mentha piperita significantly improved the pathological changes of sensitised rats. The improvement effects of higher concentrations of the Au NPs@Mentha piperita extract were significantly more than those of dexamethasone. The improvement effects of Au NPs@Mentha piperita on pathological changes, immunological and inflammatory markers in sensitised rats comparable or even more potent than dexamethasone suggests the therapeutic potential of the nanoparticle in asthma. After confirming these results in clinical trial studies, Au NPs@Mentha piperita can be used as a new drug for the treatment of asthma in humans. [ABSTRACT FROM AUTHOR]

Exopolysaccharide (EPS) from probiotic Enterococcus hirae WEHI01 was isolated and purified by anion exchange chromatography and gel chromatography, the results of which show that the EPS consists of four fractions, namely I01-1, I01-2, I01-3, and I01-4. As the main purification components, I01-2 and I01-4 were preliminarily characterized for their structure and their immunomodulatory activity was explored. The molecular weight of I01-2 was 2.28 × 104 Da, which consists mainly of galactose, and a few other sugars including glucose, arabinose, mannose, xylose, fucose, and rhamnose, while the I01-4 was composed of galactose only and has a molecular weight of 2.59 × 104 Da. Furthermore, the results of an evaluation of immunomodulatory activity revealed that I01-2 and I01-4 could improve the viability of macrophage cells, improve phagocytosis, boost NO generation, and encourage the release of cytokines including TNF-α and IL-6 in RAW 264.7 macrophages. These results imply that I01-2 and I01-4 could improve macrophage-mediated immune responses and might be useful in the production of functional food and medications. [ABSTRACT FROM AUTHOR]

Poly (3,4-ethylendioxythiophene) polystyrene sulphonate (PEDOT:PSS) is the workhorse of organic bioelectronics and is steadily gaining interest also in tissue engineering due to the opportunity to endow traditional biomaterials for scaffolds with conductive properties. Biomaterials capable of promoting neural stem cell differentiation by application of suitable electrical stimulation protocols are highly desirable in neural tissue engineering. In this study, we evaluated the adhesion, proliferation, maintenance of neural crest stemness markers and neurogenic commitment of neural crest-derived human dental pulp stem cells (hDPSCs) cultured on PEDOT:PSS nanostructured thin films deposited either by spin coating (SC-PEDOT) or by electropolymerization (ED-PEDOT). In addition, we evaluated the immunomodulatory properties of hDPSCs on PEDOT:PSS by investigating the expression and maintenance of the Fas ligand (FasL). We found that both SC-PEDOT and ED-PEDOT thin films supported hDPSCs adhesion and proliferation; however, the number of cells on the ED-PEDOT after 1 week of culture was significantly higher than that on SCPEDOT. To be noted, both PEDOT:PSS films did not affect the stemness phenotype of hDPSCs, as indicated by the maintenance of the neural crest markers Nestin and SOX10. Interestingly, neurogenic induction was clearly promoted on ED-PEDOT, as indicated by the strong expression of MAP-2 and ß--Tubulin-III as well as evident cytoskeletal reorganisation and appreciable morphology shift towards a neuronal-like shape. In addition, strong FasL expression was detected on both undifferentiated or undergoing neurogenic commitment hDPSCs, suggesting that ED-PEDOT supports the expression and maintenance of FasL under both expansion and differentiation conditions. [ABSTRACT FROM AUTHOR]

Background: Despite promising results in clinical studies, the mechanism for the beneficial effects of allogenic cell-based therapies remains unclear. Macrophages are not only critical mediators of inflammation but also critical players in cardiac remodeling. We hypothesized that transplanted allogenic rat cardiac progenitor cells (rCPCs) augment T-regulatory cells which ultimately promote proliferation of M2 like macrophages by an as-yet undefined mechanism.Methods and Results: To test this hypothesis, we used crossover rat strains for exploring the mechanism of myocardial repair by allogenic CPCs. Human CPCs (hCPCs) were isolated from adult patients undergoing coronary artery bypass grafting, and rat CPCs (rCPCs) were isolated from male Wistar-Kyoto (WKY) rat hearts. Allogenic rCPCs suppressed the proliferation of T-cells observed in mixed lymphocyte reactions in vitro. Transplanted syngeneic or allogeneic rCPCs significantly increased cardiac function in a rat myocardial infarct (MI) model, whereas xenogeneic CPCs did not. Allogeneic rCPCs stimulated immunomodulatory responses by specifically increasing T-regulatory cells and M2 polarization, while maintaining their cardiac recovery potential and safety profile. Mechanistically, we confirmed the inactivation of NF-kB in Treg cells and increased M2 macrophages in the myocardium after MI by transplanted CPCs derived GDF15 and it's uptake by CD48 receptor on immune cells.Conclusion: Collectively, these findings strongly support the active immunomodulatory properties and robust therapeutic potential of allogenic CPCs in post-MI cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Alpha-lipoic acid is one of the most powerful antioxidants used in both humans and animals. Many of its effects were proven: antioxidant, antidiabetic, anti-inflammatory, immunomodulatory, analgesic, as a growth promoter. Numerous clinical studies showed the effectiveness of alpha-lipoic acid in diseases in which the antioxidant balance was disturbed. Alpha-lipoic acid reduces the complications of diabetes such as neuropathy, nephropathy, retinopathy, and vascular damage. It improves insulin resistance. In veterinary practice, alpha-lipoic acid is used as a component in supplements for dogs, cats, pigs, and birds. The aim of this review is to present new data about its therapeutic application. [ABSTRACT FROM AUTHOR]

Background: Extracts obtained from different Betonica species have been shown to possess important biological properties. The present study aimed to investigate the cytotoxicity, antitumor and immunomodulatory potential of the endemic plant Betonica bulgarica (Lamiaceae) and thus, reveal new aspects of its biological activity. Methods: Methanolic extract obtained from inflorescences was analyzed for cytotoxicity against mammalian cell lines. The antitumor potential of the sample was determined using human cervical and lung adenocarcinoma cells (HeLa and A549). Programmed cell death-inducing effects against HeLa cells and peripheral blood lymphocytes, as well as immunomodulatory properties of the extract were determined by flow cytometry analysis. Results: The research results demonstrated that the extract has significant inhibitory potential against HeLa cells (mean IC50 value 119.2 μg/mL). The sample selectively induced apoptotic death in tumor cells. Cytotoxic effects towards mouse cell lines were detected following treatment with high concentrations of Betonica bulgarica extract (200 and 250 μg/mL). Twenty-four-hour ex vivo incubation of peripheral blood leucocytes in growth medium containing plant extract induced prominent effects in distinct immune cell populations. They included elevated levels of CD25+ and CD56+ T cells' lymphocytes, particularly CD4+CD25+ and CD8+CD56+ cells. Conclusions: The present study demonstrates that Betonica bulgarica inflorescence extract possesses potential beneficial antitumor and immunomodulatory activity and could serve as a source of bioactive compounds with biomedical application. [ABSTRACT FROM AUTHOR]

Poly (3,4-ethylendioxythiophene) polystyrene sulphonate (PEDOT:PSS) is the workhorse of organic bioelectronics and is steadily gaining interest also in tissue engineering due to the opportunity to endow traditional biomaterials for scaffolds with conductive properties. Biomaterials capable of promoting neural stem cell differentiation by application of suitable electrical stimulation protocols are highly desirable in neural tissue engineering. In this study, we evaluated the adhesion, proliferation, maintenance of neural crest stemness markers and neurogenic commitment of neural crest-derived human dental pulp stem cells (hDPSCs) cultured on PEDOT:PSS nanostructured thin films deposited either by spin coating (SC-PEDOT) or by electropolymerization (ED-PEDOT). In addition, we evaluated the immunomodulatory properties of hDPSCs on PEDOT:PSS by investigating the expression and maintenance of the Fas ligand (FasL). We found that both SC-PEDOT and ED-PEDOT thin films supported hDPSCs adhesion and proliferation; however, the number of cells on the ED-PEDOT after 1 week of culture was significantly higher than that on SC-PEDOT. To be noted, both PEDOT:PSS films did not affect the stemness phenotype of hDPSCs, as indicated by the maintenance of the neural crest markers Nestin and SOX10. Interestingly, neurogenic induction was clearly promoted on ED-PEDOT, as indicated by the strong expression of MAP-2 and β—Tubulin-III as well as evident cytoskeletal reorganisation and appreciable morphology shift towards a neuronal-like shape. In addition, strong FasL expression was detected on both undifferentiated or undergoing neurogenic commitment hDPSCs, suggesting that ED-PEDOT supports the expression and maintenance of FasL under both expansion and differentiation conditions.

Immune system modulation is an intriguing part of scientific research. It is well established that the immune system plays a crucial role in orchestrating cellular and molecular key mediators, thus establishing a powerful defense barrier against infectious pathogens. Gut microbiota represent a complex community of approximately a hundred trillion microorganisms that live in the mammalian gastrointestinal (GI) tract, contributing to the maintenance of gut homeostasis via regulation of the innate and adaptive immune responses. However, impairment in the crosstalk between intestinal immunity and gut microbiota may reflect on detrimental health issues. In this context, many studies have indicated that probiotics and their bioactive compounds, such as bacteriocins and short chain fatty acids (SCFAs), display distinct immunomodulatory properties through which they suppress inflammation and enhance the restoration of microbial diversity in pathological states. This review highlights the fundamental features of probiotics, bacteriocins, and SCFAs, which make them ideal therapeutic agents for the amelioration of inflammatory and autoimmune diseases. It also describes their underlying mechanisms on gut microbiota modulation and emphasizes how they influence the function of immune cells involved in regulating gut homeostasis. Finally, it discusses the future perspectives and challenges of their administration to individuals.

Background Neonatal sepsis remains a major global health challenge, contributing significantly to morbidity and mortality in term neonates. Despite advancements in neonatal care, the early identification and prevention of sepsis continue to pose challenges. Emerging research suggests that vitamin D, traditionally recognized for its role in bone health, also plays a crucial role in immune regulation. Objectives To evaluate and compare serum vitamin D levels in term neonates with sepsis and without sepsis. Methods The study included 60-term neonates, with 30 neonates diagnosed with sepsis as cases and 30 healthy-term neonates as controls. Detailed history and clinical examination were performed for all subjects. Sepsis was diagnosed based on clinical and laboratory criteria. Serum vitamin D levels were assessed using the chemiluminescent microparticle immunoassay (CMIA) technique. Results The mean serum vitamin D levels in the sepsis group were significantly lower (16.0 ng/mL ± 10.5) compared to the control group (29.07 ng/mL ± 8.4) with a p-value <0.01. There was no significant difference in gender distribution (p=0.79), socioeconomic status (p=0.752), or maternal age (p=0.349) between the groups. Significant differences were found in the mode of delivery (p=0.037), presence of meconium-stained liquor (p=0.001), intrapartum antibiotic administration (p=0.0006), and resuscitation requirements (p=0.0004). APGAR scores at one minute were significantly lower in the sepsis group (p=0.001). Clinical features among sepsis cases included poor activity (40%), tachypnoea (46.6%), tachycardia (43.3%), and hyperthermia (40%). Conclusion A strong association between vitamin D deficiency and the severity of sepsis was observed, with deficient neonates showing higher rates of severe, early-onset sepsis., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Sub-Committee issued approval IESC/PGS2022/28. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Dua et al.)

The ability of MSCs to modulate the inflammatory environment is well recognized, but understanding the molecular mechanisms responsible for these properties is still far from complete. Prostaglandin E2 (PGE2), a product of the cyclooxygenase 2 (COX-2) pathway, is indicated as one of the key mediators in the immunomodulatory effect of MSCs. Due to the pleiotropic effect of this molecule, determining its role in particular intercellular interactions and aspects of cell functioning is very difficult. In this article, the authors attempt to summarize the previous observations regarding the role of PGE2 and COX-2 in the immunomodulatory properties and other vital functions of MSCs. So far, the most consistent results relate to the inhibitory effect of MSC-derived PGE2 on the early maturation of dendritic cells, suppressive effect on the proliferation of activated lymphocytes, and stimulatory effect on the differentiation of macrophages into M2 phenotype. Additionally, COX-2/PGE2 plays an important role in maintaining the basic life functions of MSCs, such as the ability to proliferate, migrate and differentiate, and it also positively affects the formation of niches that are conducive to both hematopoiesis and carcinogenesis.

Traditional medicinal plants have been used for centuries for their immunomodulatory properties and therapeutic potentials. The present study aims to investigate the immunomodulatory constituents from traditional medicinal plant, Tinospora cordifolia (willd.). Our study resulted in the isolation of new compound, 27-hydroxy octacosyl ferulate (1) along with eleven known compounds (2 − 12). The structures of the isolated compounds were characterized by combination of NMR (1D and 2D) and Mass spectroscopic methods. The hemisynthesis of compound 12 (ferulic acid) yielded (12a-12d and 12e-12 m) derivatives. Further, the isolated compounds and synthesized derivatives were assessed for their immunomodulatory potentials by evaluating their cytotoxicity and pro-inflammatory effects against macrophage cells (IL-6) and DC activation markers (CD 11c and 86). The biological results indicated that crude extract displayed potent immunomodulatory activity while isolated compounds and synthetic analogues showed moderate activity. Among the tested compounds, new compound (1), quercetin (10) and derivatives 12b , 12c found to be non-cytotoxic and displayed immunomodulatory potentials. Therefore, these compounds can be studied for autoimmunity and other immune suppressing conditions. [Display omitted] [ABSTRACT FROM AUTHOR]

Exopolysaccharide (EPS) from probiotic Enterococcus hirae WEHI01 was isolated and purified by anion exchange chromatography and gel chromatography, the results of which show that the EPS consists of four fractions, namely I01-1, I01-2, I01-3, and I01-4. As the main purification components, I01-2 and I01-4 were preliminarily characterized for their structure and their immunomodulatory activity was explored. The molecular weight of I01-2 was 2.28 × 104 Da, which consists mainly of galactose, and a few other sugars including glucose, arabinose, mannose, xylose, fucose, and rhamnose, while the I01-4 was composed of galactose only and has a molecular weight of 2.59 × 104 Da. Furthermore, the results of an evaluation of immunomodulatory activity revealed that I01-2 and I01-4 could improve the viability of macrophage cells, improve phagocytosis, boost NO generation, and encourage the release of cytokines including TNF-α and IL-6 in RAW 264.7 macrophages. These results imply that I01-2 and I01-4 could improve macrophage-mediated immune responses and might be useful in the production of functional food and medications.

Background: Extracts obtained from different Betonica species have been shown to possess important biological properties. The present study aimed to investigate the cytotoxicity, antitumor and immunomodulatory potential of the endemic plant Betonica bulgarica (Lamiaceae) and thus, reveal new aspects of its biological activity. Methods: Methanolic extract obtained from inflorescences was analyzed for cytotoxicity against mammalian cell lines. The antitumor potential of the sample was determined using human cervical and lung adenocarcinoma cells (HeLa and A549). Programmed cell death-inducing effects against HeLa cells and peripheral blood lymphocytes, as well as immunomodulatory properties of the extract were determined by flow cytometry analysis. Results: The research results demonstrated that the extract has significant inhibitory potential against HeLa cells (mean IC50 value 119.2 μg/mL). The sample selectively induced apoptotic death in tumor cells. Cytotoxic effects towards mouse cell lines were detected following treatment with high concentrations of Betonica bulgarica extract (200 and 250 μg/mL). Twenty-four-hour ex vivo incubation of peripheral blood leucocytes in growth medium containing plant extract induced prominent effects in distinct immune cell populations. They included elevated levels of CD25+ and CD56+ T cells’ lymphocytes, particularly CD4+CD25+ and CD8+CD56+ cells. Conclusions: The present study demonstrates that Betonica bulgarica inflorescence extract possesses potential beneficial antitumor and immunomodulatory activity and could serve as a source of bioactive compounds with biomedical application.