Immunomodulatory Activity Research Articles

In Vitro Interaction Between Yeast Extracellular Vesicles and Human Monocyte-Derived Dendritic Cells.

Extracellular vesicles (EVs) are lipid-bound particles produced by a wide variety of cells from different biological species. EVs can carry molecules, such as nucleic acids and metabolites, and are involved in cell functioning, communication, and signaling. Recent literature reported that pathogenic or commensal yeast strains can produce EVs targeting the host's immune system and exerting immunomodulatory actions. In humans, yeast EVs can be endocytosed by dendritic cells (DCs), characterized by phagocyting and migrating capabilities with the role of capturing antigens to present to T lymphocytes, triggering the immune response. Physiological or disease-associated immunosenescence impairs both DC functionality and gut microbiota; thus investigating the interaction between commensal microorganisms and the host's immune system would help elucidate the impact of aging on the immune system-microbiota interplay. We hereby present a protocol for the incubation of in vitro-generated human monocyte-derived DCs with EVs purified from different yeast strains isolated from fermented milk. The protocol includes flow cytometry analysis on DC activation markers and endocytosis assay.

CaCO3-complexed pH-responsive nanoparticles encapsulating mitoxantrone and celastrol enhance tumor chemoimmunotherapy

Modulating the immunosuppressive tumor microenvironment (TME) while enhancing antitumor immune responses is a promising strategy. In this study, we designed an acid-sensitive nanosystem (MCCaNPs) to demonstrate effective immunotherapy against cancer through the systemic delivery of immune-stimulating chemotherapy combinations. A pH-responsive nanoplatform containing CaCO3 was prepared by the double emulsion method, and mitoxantrone (MIT) and celastrol (CEL) were simultaneously encapsulated as immunogenic cell death (ICD) inducers. Due to the acid responsiveness of CaCO3, the nanoparticles rapidly consume H+ to relieve the acidic tumor microenvironment and explosively release CEL and MIT, showing inherent immunomodulatory activity in collaborative tumor chemoimmunotherapy. MIT and CEL synergistically trigger stronger ICD by inducing tumor cells to release calreticulin (CRT), high mobility group box 1 protein (HMGB1). Following the intravenous administration of MCCaNPs, the local tumor microenvironment(TME) was reprogrammed in mice-bearing tumors. This reprogramming was characterized by a significant increase in the density of tumor-infiltrating cytotoxic T lymphocytes(CTLs), ultimately prolonging survival. Therefore, this research proposes a promising approach to trigger immunogenic cell death collaboratively, aiming to boost the tumor CTLs infiltration for anticancer immunotherapy.

Evaluation of attenuated Salmonella Typhimurium (STMΔznuABC) anticancer activity on canine mammary cancer-associated fibroblasts

Bacteria-mediated treatments gained increasing attention as alternative therapies against tumors. An attenuated mutant strain of Salmonella enterica serovar Typhimurium (STMΔznuABC) has recently been considered as a potential new anti-cancer strategy. However, it is unclear whether this activity is tumor-induced or species-specific, and no data are available regarding STMΔznuABC on canine mammary tumors (CMTs). This study aimed to investigate the ability of STMΔznuABC in modulating the response of CMTs, focusing on cancer-associated fibroblasts. Four CMT cell lines (CF33, TM51, TM52 TM53) were treated with STMΔznuABC. Then, antiproliferative activity (MTT assay), bacterial invasion, and CMT cell lines gene expression analysis (RT-qPCR) of genes involved in immune response and cancer aggressiveness were evaluated. STMΔznuABC penetrated in TM51, TM52, TM53, and CF33 cell lines, causing a significant reduction of cell viability. Moreover, the expression of several genes was significantly modulated in all CMT cell lines: STMΔznuABC infection determined a significant up-regulation of CXCL8, IL18, IL10, TLR4 and RAD51, while CD14, IL6, CXCR4, P53, PTEN, STAT5, TLR5 and TGFB were downregulated in TM53. In CF33, CXCL8 and P53 were upregulated, while MYD88, MD2, IL18, TLR4,5, TGFB were downregulated. In TM52, CXCL8, CD44 and MD2 were upregulated and PTEN was downregulated, while in TM51 CXCL8, CD44 and ErbB2 were downregulated. We demonstrated the anti-proliferative and immuno-modulatory activity of STMΔznuABC in CMTs, paving the way for potential new anti-cancer treatments.

Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances

BackgroundNeurodegenerative diseases (NDDs) are a diverse group of neurological disorders with progressive neuronal loss at specific brain regions, leading to impaired cognitive functioning, loss of neuroplasticity, severe neurological impairment, and dementia. The incidence of neurodegenerative diseases is increasing at an alarming rate with current treatments struggling to barely prolong the inevitable. The desperation to discover a therapeutic agent to treat neurodegenerative diseases and to aid in the process of healthy recovery has opened a gateway into natural pigments. HypothesisThe xanthophyll pigment lutein may bear the potential as a therapeutic agent against NDDs. ResultsLutein plays an important role in brain development, cognitive functioning, and improving neuroplasticity. In vitro and in vivo studies revealed the neuroprotective properties of lutein against NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia. The neuroprotective effect of lutein is evidenced by the reduction of free radicals and the simultaneous strengthening of the endogenous antioxidant systems by activating the NRF-2/ERK/AKT pathway. Further, it effectively suppressed mitochondrial aberrations, excitotoxicity, overaccumulation of metals, and its resultant complications. The immunomodulatory activity of lutein prevents neuroinflammation by hindering NF-κB nuclear translocation, regulation of NIK/IKK, PI3K/AKT, MAPK/ERK, JNK pathways, and ICAM-1 downregulation. Lutein also rescued the dysregulated cholinergic system and resolved memory defects. Along with its neuroprotective properties, lutein also improved neuroplasticity by enabling neurogenesis through increased GAP-43, NCAM, and BDNF levels. ConclusionLutein exhibits strong neuroprotective activities against various NDDs. Though the investigations are in the exploratory phase, this review presents the consolidation of scattered evidence of the neuroprotective properties of lutein and urges its further exploration in clinical studies.

A novel arabinogalactan extracted from Epiphyllum oxypetalum (DC.) Haw improves the immunity and gut microbiota in cyclophosphamide‐induced immunosuppressed mice

AbstractA novel type I arabinogalactan (AG‐I) polysaccharide (EPS) from Epiphyllum oxypetalum (DC.) Haw's flowers is hypothesized to possess immunomodulatory activity. This study investigated EPS's effects on immune functions and its potential mechanism for enhancing intestinal health in immunosuppressed mice. The results showed that supplementing EPS significantly alleviated immune organ damage, increased the thymus index (p < 0.01), and regulated the key immune factors, including the tumor necrosis factor‐alpha (TNF‐α), immunoglobulin A (IgA), and complement 3 (C3) in the liver (p < 0.05). EPS promoted the expression of intestinal immune barrier and chemical barrier proteins such as interferon‐γ (IFN‐γ) and mucin 2 (MUC2) (p < 0.05), effectively repairing intestinal damage. EPS improved the diversity and structure of intestinal microbiota in immunosuppressed mice (p < 0.05) and significantly altered the abundance of intestinal immune‐related microbial taxa, including Lactobacillaceae and Lactobacillus (p < 0.01). Furthermore, EPS supplementation altered intestinal lactic acid metabolism, significantly increasing lactic acid levels by up to 3.4‐fold (p < 0.01), and enhanced the expression of Gpr81, Wnt3a, and β‐catenin proteins at the bottom of the colonic crypts, which may repair the intestinal physical barrier. Overall, EPS represents a novel AG‐I immunomodulatory dietary polysaccharide that enhances immunity and improves gut health.

Targeting heparanase/heparan sulfate proteoglycans by non‐anticoagulant heparins: Opportunities for innovative therapeutic approaches in sarcomas

AbstractSarcomas are a heterogeneous group of aggressive mesenchymal malignancies. They account for 1% of all tumors in the general population and 15–20% in pediatric age and young adults. Despite differences in histology and pathobiology, the diverse types of sarcomas are traditionally managed with a common multi‐modal approach including surgery, radiotherapy, and aggressive polychemotherapy. Unfortunately, the prognosis for advanced or recurrent disease remains poor. Moreover, the disease rarity and a high cellular, molecular, and genetic/epigenetic heterogeneity make identification of therapeutic targets challenging. Therefore it remains an urgent need to identify effective therapies to improve patients' outcome. Common or peculiar biological motifs including deregulation of growth factor signaling, proangiogenic and promigratory pathways, tumor‐microenviroment interactions, transcriptional and epigenetic machinery, and differentiation program, provide actionable dependencies exploitable for therapeutic intervention. Among these, a deregulated heparan sulfate proteoglycan system due to aberrant expression of key components as well as structural/functional modifications mediated by endosulfatases and the endoβ‐d‐glycosidase heparanase, is emerging as a crucial player in tumor growth and progression and as a valuable therapeutic target across different sarcoma subtypes. In preclinical studies, non‐anticoagulant heparins have been shown to counteract the growth and metastatic dissemination of various sarcoma models according to their heparan sulfate mimetic and anti‐heparanase activities. Heparin derivatives also improved the anti‐sarcoma efficacy of molecularly targeted agents and cytotoxic drugs. In this minireview, we summarize the current knowledge about the interplay between the heparanase/heparan sulfate proteoglycan system and pathways involved in sarcomagenesis and disease progression. We illustrate the current understanding of the mechanisms of action of non‐anticoagulant heparins and the contribution of their anti‐heparanase, anti‐receptor tyrosine kinase, and likely immunomodulatory activities to their anti‐sarcoma effects. Finally, we discuss a few aspects worthy of exploration highlighting how elucidation of mechanisms underpinning antitumor activities of non‐anticoagulant heparin derivatives in the different sarcoma biological contexts may suggest new vulnerabilities and therapeutic approaches.

The impact of achieving remission in inflammatory bowel disease on plasma matrix -carboxyglutamate protein levels

Matrix -carboxyglutamic acid (MGLA) protein is a vitamin K dependent peptide which contributes to the immunomodulatory activity of mesenchymal stromal cells. There is a possible association between MGLA protein and inflammatory bowel disease (IBD) which is divided into Crohn’s disease (CD) and ulcerative colitis (UC). However, little is known about the clinical utility of MGLA protein in IBD patients. This study aimed to assess the impact of achieving remission on the serum MGLA protein levels in IBD patients. This prospective observational study included 60 newly diagnosed IBD patients. All patients were subjected to full clinical, laboratory, radiological, and histopathological assessment of IBD at baseline and six months after initiating treatment. Serum MGLA protein level was assessed using an enzyme-linked immunosorbent assay. There were 29 (48.3%) UC cases and 31 (51.67%) CD cases. We observed a significant decrease in serum MGLA protein levels after 6 months of treatment compared to pretreatment values in UC patients (120.490 ± 26.273 vs. 26.320 ± 17.378 nmol/L, p<0.001) and CD patients (125.576 ± 28.208 vs. 28.520 ± 18.443 nmol/L, p<0.001). Serum MGLA protein levels were significantly higher in non-remittent patients compared to remittent UC patients before treatment (142.556 ± 17.096 vs. 110.560 ± 23.659 nmol/L, p<0.001) and after six months of treatment (51.222 ± 4.410 vs. 15.114 ± 3.302 nmol/L, p<0.001). Serum MGLA protein levels were significantly higher in non-remittent patients compared to remittent CD patients before treatment (150.727 ± 7.198 vs. 111.743 ± 25.718 nmol/L, p<0.001) and after six months of treatment (52.182 ± 5.269 vs. 15.506 ± 4.475 nmol/L, p<0.001). This response was irrespective of the therapeutic modality. In conclusion, achievement of remission in IBD patients resulted in a significant decrease in serum MGLA protein levels.

Sulfated Chinese yam polysaccharide exert anti-inflammatory potential via MAPK/NF-κB signaling pathways in a co-culture system and LPS-induced acute inflammatory mice model.

Our previous study has demonstrated that sulfated Chinese yam polysaccharide (SCYP) can improve immunomodulatory activity in Raw 264.7 cells. However, its anti-inflammatory is little known. In this study, the anti-inflammatory effects of SCYP were systematically investigated via the Lipopolysaccharides (LPS)-induced Raw264.7 cell model, Caco-2/Raw264.7 co-culture system, and acute inflammation mice model. The results suggested SCYP promoted the cell proliferation and have no toxicity in Raw264.7 and Caco-2 cells at the concentration of 200µg/mL. Moreover, when treated with SCYP, the production of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) reduced significantly in Raw264.7 via the MAPK/NF-κB pathway. In the Caco-2/Raw264.7 co-cultured system, SCYP could regulate inflammation reaction by improving intestinal barrier, which might prevent systemic inflammation. Further, systemic inflammation was alleviated by SCYP in LPS-induced acute inflammation mice through MAPK/NF-κB pathway. PRACTICAL APPLICATION: These results supported that SCYP may be used as an anti-inflammation agent in the functional food field.

Anticancer Effects of BAF312 (Siponimod) in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is a lethal disease that is the fifth leading cause of cancer-related death in women. BAF312 (siponimod) is a potent and selective sphingosine-1-phosphate (S1P) receptor modulator that has been approved as a treatment for multiple sclerosis. In addition to its immunomodulatory action, BAF312 shows preclinical antitumor effects in several cancer types. This study sought to determine whether BAF312 had anticancer properties against EOC using in vitro and in vivo models. EOC cell lines A2780, SKOV3ip1, A2780-CP20, and SKOV3-TR were treated with BAF312 and tested for cell proliferation, apoptosis, and migration using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence-activated cell sorting, and migration assays. We investigated the expression of sphingosine-1-phosphate receptor 1 (S1PR1) in most EOC cell lines through western blot analysis. To investigate potential mechanisms, western blot analysis was used to assess the expression of AKT serine/threonine kinase 1 (AKT) and extracellular-regulated kinase (ERK) after BAF312 treatment. We also created poly(D,L-lactide-co-glycolide) nanoparticles encapsulating BAF312 (PLGA-NP-BAF312) for in vivo therapy. The average size and zeta potential of PLGA-NP-BAF312 were determined using dynamic light scattering. The therapeutic efficacy of PLGA-NP-BAF312 was tested in an A2780 tumor-bearing orthotopic mouse model of EOC. S1PR1 was overexpressed in most EOC cell lines. BAF312 significantly reduced cell proliferation and migration while inducing significant apoptosis in all EOC cell lines. PLGA-NP-BAF312 treatment significantly reduced tumor weights in A2780 tumor-bearing mice. Furthermore, the anticancer effects of BAF312 were associated with reduced phosphorylation of ERK and AKT. Our findings show that BAF312 has significant anticancer effects in EOC cells by inhibiting the ERK and AKT pathways, and might potentially be used to treat EOCs.

Regional Variations In The Immunohistochemical Expression Of P75 NGF Receptors Between Term And Post-Term Human Placenta

Background: The placenta has lately attracted increased attention due to its potential as a significant source of many types of stem cells, such as trophoblastic, hematopoietic, epithelial, and mesenchymal stem cells (MSCs). Placental cells are readily and ethically obtainable. In addition, the human placenta has the potential to provide a significant quantity of stem cells that can be readily isolated, expanded, and differentiated into several kinds of cells. Both the maternal and the fetal components of MSCs are present in the human placenta. Previous investigations have found that the origin of mesenchymal stem cells has a significant impact on their capacity to treat diseases. As a result, placental MSCs have a lot of potential for therapeutic use. Compared to the immunomodulatory activity of MSCs derived from mothers, fetal MSCs have a higher capacity to promote immunological health. The p75 protein has been demonstrated to be the most effective marker for the isolation and identification of human bone marrow-derived mesenchymal stem cells. CD271 was considered a versatile marker that would allow the isolation and culture of multipotent stem cells derived from mesenchymal tissue. No prior work reported P75 NGFR utilized in placental tissues as a marker for mesenchymal stem cells in connection to various gestational ages (term, and post-term) and diverse placental locations including (chorionic plate and placental villi sides).

Low molecular weight polysaccharide of Tremella fuciformis exhibits stronger antioxidant and immunomodulatory activities than high molecular weight polysaccharide

Low molecular weight polysaccharides had higher bio-activity and bioavailability compared to ultra-high molecular weight polysaccharides, this study aimed to obtain low molecular weight polysaccharides from Tremella fuciformis (TFLP) by using high-temperature and high-pressure assisted hydrochloric acid method to degrade Tremella fuciformis polysaccharides (TFP), and the structural characteristics, in vivo antioxidant and immune enhancing activities of TFP and TFLP was explored through Caenorhabditis elegans (C. elegans) and mice model. It was found that TFP and TFLP were acidic polysaccharides with molecular weights of 2238 kDa and 3 kDa, respectively. The glycosidic bonding of TFP and TFLP was mainly composed of different configurations of mannopyranose. TFP and TFLP had excellent in vivo antioxidant activity and stress resistance by regulating the mRNA transcription level and metabolites in C. elegans. Results also showed that TFP and TFLP could enhance the antioxidant capacity and immunity of serum, spleen and small intestine tissues in normal mice and cyclophosphamide-induced immunosuppressive mice through regulating the relative transcription and expression levels of anti-inflammatory related signaling factors, and it has found that TFLP showed better immune enhancement and antioxidant activity than TFP. In addition, Akkermansia, Bacteroides and Alloprevotella were characteristic bacteria at the genus level in immunosuppressed mice intervened with TFLP, with a significant increase in relative abundance. The content of SCFAs significantly increased in immunosuppressed mice by TFLP. These results indicated that TFP and TFLP had potential in vivo antioxidant and immune enhancing activities.

Metabolomics and 16S rDNA sequencing of intestinal flora reveal the regulation of Sparassis latifolia polysaccharides on splenic immune function in lead-exposed mice

Sparassis latifolia polysaccharides (SLPs) have immunomodulatory activity and lead excretion ability, but its regulatory mechanism through the gut microbiota-spleen axis has not been elucidated. In this study, spleen metabolomics and intestinal flora sequencing were combined to explore the regulatory mechanism of SLPs on spleen immune function in lead-exposed mice. The results showed that SLPs effectively reduced spleen lead content, alleviated spleen enlargement and oxidative stress. SLPs changed glycerophospholipid metabolism, increased lysophosphatidylcholine content and inhibited the expression of G2A, ERK2 and NF-kB genes and the phosphorylation of ERK2 and NF-kB in lead-exposed mice. Furthermore, SLPs inhibited potential intestinal pathogens such as Clostridium_sensu_stricto_1, Lachnospiraceae, Oscillospiraceae and Alistipes_indistinctus, which were positively correlated with phosphatidylethanolamine metabolites. In addition, SLPs reduced the spleen tissue damage of lead-exposed mice by co-housing, and reduced the relative abundance of Clostridium_sensu_stricto_1, Prevotellaceae, and RF39, which were positively correlated with spleen enlargement, and inhibited the expression of ERK2/NF-κB signaling pathway-related genes such as G2A, ERK2 and Fas. In summary, SLPs can reduce the relative abundance of pathogenic microorganisms by regulating the structure of intestinal flora, regulate the glycerophospholipid metabolism of spleen in lead-exposed mice, alleviate oxidative damage and inflammatory response, and restore spleen immune function.

Distinctive Immune Signatures Driven by Structural Alterations in Desmuramylpeptide NOD2 Agonists.

Herein we report on the design, synthesis and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists. The structural prerequisites that shape both physicochemical and immunomodulatory profiles of desmuramylpeptide NOD2 agonists have been delineated. Within this context, we identified 3, a butyrylated desmuramylpeptide, as a potent in vitro NOD2 agonist (EC50 = 4.6 nM), exhibiting an almost 17-fold enhancement in potency compared to its unsubstituted counterpart 1 (EC50 = 77.0 nM). The novel set of desmuramylpeptides demonstrate unique in vitro immunomodulatory activities. They elicited cytokine production in peripheral blood mononuclear cells (PBMCs), both alone and in conjunction with lipopolysaccharide (LPS). The spermine-decorated 32 also stimulated the LPS-induced cytotoxic activity (2.95-fold) of PBMCs against K562 cancer cells. Notably, the cholesterol-conjugate 26 displayed anti-inflammatory actions, highlighted by its capacity to convert the inflammatory monocyte subset into an anti-inflammatory phenotype. Finally, the eicosapentaenoylated derivative 23 augmented antigen presentation by mouse bone marrow-derived dendritic cells (BMDCs), thus highlighting its potential as a vaccine adjuvant.

Halocins and C50 Carotenoids from Haloarchaea: Potential Natural Tools against Cancer.

Haloarchaea are a group of moderate and extreme halophilic microorganisms, belonging to the Archaea domain, that constitute relevant microbial communities in salty environments like coastal and inland salted ponds, marshes, salty lagoons, etc. They can survive in stress conditions such as high salinity and, therefore, high ionic strength, high doses of ultraviolet radiation (UV), high temperature, and extreme pH values. Consequently, most of the species can be considered polyextremophiles owing to their ability to respond to the multiple extreme conditions characterizing their natural habitats. They cope with those stresses thanks to several molecular and metabolic adaptations. Thus, some of the molecules produced by haloarchaea show significantly different biological activities and physicochemical properties compared to their bacterial counterparts. Recent studies have revealed promising applications in biotechnology and medicine for these biomolecules. Among haloarchaeal biomolecules, rare natural pigments (C50 carotenoids) and small peptides called halocins and microhalocins have attracted attention worldwide due to their effects on animal and human commercial tumoral cells, apart from the role as antibiotics described for halocins or the immunomodulatory activity reported from C50 carotenoids like bacterioruberin. This review summarizes recent knowledge on these two types of biomolecules in connection with cancer to shed new light on the design of drugs and new therapies based on natural compounds.

Phytochemical Analysis and In Vitro Effects on Isolated Murine Lymphocytes and Macrophages of Polymeric Micelles Loaded with Cycloartane Saponin

Triterpenoid saponins from the Astragalus species possess valuable effects (cytotoxic, adjuvant, hepatoprotective, neuroprotective, antiviral, etc.). Some also have immunomodulatory activities. Astragalus glycyphyllos is distributed in Bulgaria and mainly accumulates cycloartane saponins. From the overground parts of the species, a triterpenoid cyloartane-type saponin (AGOS3) was isolated by different chromatographic techniques. A quantitative LC-MS method for the determination of the saponin was developed and validated. Further, the saponin was loaded in copolymeric micelles based on triblock copolymers of polyethylene oxide and polypropylene oxide (Pluronics). The LC-MS method was applied on the developed micelles to determine their loading degrees. Afterwards, the possible pharmacological effects of free and encapsulated in polymeric nanoparticles of triterpenoid saponin (1, 5, 10, 25, 50, and 100 µg/mL) were evaluated in isolated murine macrophages and lymphocytes in vitro. Free AGOS3 stimulated proliferation only at the highest tested concentrations (50–100 µg/mL), and the effect was more evident in isolated macrophages. Interestingly, AGOS3-loaded polymeric micelles caused concentration dependency and statistically significant increases in the proliferation of both isolated lymphocytes and macrophages, even at a lower concentration (10 µg/mL). These results could serve as the basis for further research on the immunomodulatory effect of this saponin.

Probio-Ichnos: A Database of Microorganisms with In Vitro Probiotic Properties.

Probiotics are live microorganisms that, when consumed in adequate amounts, exert health benefits on the host by regulating intestinal and extraintestinal homeostasis. Common probiotic microorganisms include lactic acid bacteria (LAB), yeasts, and Bacillus species. Here, we present Probio-ichnos, the first manually curated, literature-based database that collects and comprehensively presents information on the microbial strains exhibiting in vitro probiotic characteristics (i.e., resistance to acid and bile, attachment to host epithelia, as well as antimicrobial, immunomodulatory, antiproliferative, and antioxidant activity), derived from human, animal or plant microbiota, fermented dairy or non-dairy food products, and environmental sources. Employing a rigorous methodology, we conducted a systematic search of the PubMed database utilizing the keyword 'probiotic' within the abstracts or titles, resulting in a total of 27,715 studies. Upon further manual filtering, 2207 studies presenting in vitro experiments and elucidating strain-specific probiotic attributes were collected and used for data extraction. The Probio-ichnos database consists of 12,993 entries on the in vitro probiotic characteristics of 11,202 distinct strains belonging to 470 species and 143 genera. Data are presented using a binary categorization approach for the presence of probiotic attributes according to the authors' conclusions. Additionally, information about the availability of the whole-genome sequence (WGS) of strains is included in the database. Overall, the Probio-ichnos database aims to streamline the navigation of the available literature to facilitate targeted validation and comparative investigation of the probiotic properties of the microbial strains.

The polysaccharide from Aralia continentalis Kitagawa enhances immune responses via activating the MAPKs and NF-κB signaling pathways in RAW 264.7 macrophages

BackgroundPolysaccharides derived from Aralia continentalis Kitagawa possess excellent biological properties, such as anti-tumor, antioxidant, antibacterial, lipid-lowering, and anti-inflammatory. However, the immunomodulatory effects of these polysaccharides on macrophages and their underlying mechanisms remain largely unexplored due to their complex molecular structure.ResultsThe study isolated and characterized a pure polysaccharide, namely WACP(S)-A3-b from Aralia continentalis Kitagawa to investigate its impact on RAW 264.7 cell activation. The structural analysis of WACP(S)-A3-b revealed an average molecular weight of 40.1 kDa with a pectin-like structure composed of HG and RG-I domains, primarily composed of galacturonic acid, rhamnose, galactose, fucose, and arabinose at molar ratios of 55.56: 19.60: 10.29: 7.85: 6.69; NMR found that WACP(S)-A3-b contains α-1,4-GalpA, α-1,2-Rhap, α-1,2,4-Rhap, and t-α-GalpA. Further results demonstrated that the immunomodulatory activity of WACP(S)-A3-b could enhance the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and promote the expression of interleukin-1beta (IL-1β). Additionally, WACP(S)-A3-b could activate MAPKs and NF-κB signaling pathways, thereby enhancing the ability of RAW 264.7 macrophages to release cytokines.ConclusionsThe study isolated and purified the Aralia continentalis Kitagawa stem polysaccharide, clarified the basic structure of the polysaccharide, and explored the mechanism of immune activity, which provided a theoretical basis for the structure–activity relationship of the polysaccharide.Graphical abstract

Cordyceps militaris fruit body activates myeloid dendritic cells via a Dectin-1-mediated pathway

Cordyceps militaris, an entomopathogenic fungus, has been traditionally used in East Asian medicine. Recent research indicates that the fruit bodies of C. militaris are rich in bioactive compounds, such as polysaccharides and nucleosides, which may offer health benefits. However, the specific components responsible for its immunostimulatory effects and the mechanisms involved remain unclear. This study explored the immunomodulatory activity of a fruit body extract from C. militaris, named Ryukyu-kaso (RK), and examined the effect of the β-glucan receptor Dectin-1 on bone marrow-derived dendritic cells (BMDCs). Our results demonstrated that RK, which contains 1,3-β-glucan, effectively stimulated BMDCs to secrete pro-inflammatory and immunoregulatory cytokines and upregulated surface markers indicative of maturation and activation. Notably, these immunostimulatory effects were completely absent in BMDCs derived from Dectin-1-knockout mice, confirming that Dectin-1 is crucial for RK-induced immunomodulation. These findings provide new insights into the immunostimulatory mechanisms of C. militaris and underscore the potential of RK as a natural immunomodulatory agent for various therapeutic applications.

The effect of sodium deoxyribonucleate with iron complex on the expression of surface markers of MT-4 cells infected with human immunodeficiency virus type 1 (HIV-1) (Retroviridae: Primate lentivirus group)

The persistence of immune dysfunction during therapy has serious consequences for the health of HIV-infected people. Therefore, an important direction is the search for drugs that can reduce the inflammatory potential of the immune system and serve as an additional component of antiviral therapy. Aim ‒ to study the effect of the immunomodulatory drug Sodium deoxyribonucleate with iron complex (DNA-Na-Fe) on the expression of activation markers in MT-4 cells infected with HIV-1. Expression levels of CD4, CD28, CD38, CD62L and HLA-DR proteins on the plasma membrane were measured in cells. To assess viral activity, the p24 protein was quantified by ELISA. The two cell variants with different replicative activity were analyzed. Control cells, cells with DNA-Na-Fe, infected cells and infected cells with DNA-Na-Fe were tested. Based on the results obtained, it can be concluded that antiviral activity of the drug in MT-4 cells infected with HIV-1 is associated with immunomodulatory activity that enhances the expression of membrane proteins CD4, CD28, CD38 and CD62L. Diversity in the effect of DNA-Na-Fe on the studied surface proteins expression in two cell lines indicates that they depend on the characteristics of the combined molecular biological processes occurring in cells. And the increased effects observed in a system with changes in replicative activity assumes its active participation in virus replication at the stages of virus penetration and budding. Studies have shown that DNA-Na-Fe has antiviral and immunomodulatory activity.

10-Butyl Ether Minocycline Reduced High Alcohol Consumption in a Dependence Mouse Model

ABSTRACT Alcohol use disorder (AUD) poses a significant public health concern, with limited, high-efficacy, treatment options. Our lab has demonstrated that minocycline, an antibiotic with neuroprotective and immunomodulatory properties, is effective in reducing alcohol consumption in rodent models. We then synthesized antimicrobial-free minocycline derivatives to utilize their neuroprotective and immunomodulatory activities while mitigating antibiotic-related side effects. 10-Butyl Ether Minocycline (BEM) was chosen as a lead molecule based on efficacy and physicochemical properties from the library of compounds synthesized. Here, we report that BEM significantly reduced alcohol consumption in the Chronic Intermittent Ethanol (CIE) mouse model of alcohol dependence.