T cells and macrophages jointly modulate osteogenesis of mesenchymal stromal cells.

Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.

Assessment of the biological activity of Marrubium friwaldskyanum Boiss. (Lamiaceae).

Present scientific evidences about the biological activity and potential medical application of extracts derived from Marrubium friwaldskyanum Boiss. are limited. Therefore, our study was undertaken to define several main characteristics in this regard - in vitro cytotoxicity and antitumor properties, antibacterial activity and immunomodulatory potential. Extracts were obtained from different aerial parts of Marrubium friwaldskyanum - stems, leaves and flowers. The in vitro cytotoxicity and antitumor activity of the samples were evaluated by tetrazolium salt reduction tests and Neutral red uptake assays using four human cell lines (a normal fibroblastic and three adenocarcinoma cell lines/A549, HeLa, HT-29/) and by experiments with HT-29 tumor spheroids. Antibacterial activity toward Gram-negative (Escherichia coli) and Gram-positive (Bacillus cereus) species was assessed based on estimation of minimal inhibitory and minimal bactericidal concentrations as well as longitudinal studies on bacterial viability. Ex vivo assays with normal leukocytes were performed to define potential immunomodulatory activity of the extracts. Our results demonstrated selective antitumor activity of the extracts directed against colon adenocarcinoma HT-29 cells and cervical adenocarcinoma HeLa cell line. Metabolic activity of A549 lung adenocarcinoma cells was affected only by the sample derived from flowers. M. friwaldskyanum leaf and flower extracts showed the highest activity, which included reduction of HT-29 tumor spheroid growth and viability. The studied samples exhibited antibacterial activity against both bacterial species tested. Treatment with M. friwaldskyanum extracts affected specific leukocyte populations (HLA+, CD19+, CD11b+, CD25+ cells). These results demonstrate for the first time complex biological effects of extracts derived from M. friwaldskyanum and their potential to serve as a source of valuable compounds for the pharmaceutical industry.

Emerging treatment landscape for Guillain-Barré Syndrome (GBS): what's new?

INTRODUCTION: Guillain-Barré syndrome (GBS) is a monophasic immune neuropathic disorder characterized by acute paralysis. A significant portion of patients are left with residual deficits, which presents a considerable global healthcare challenge. The precise mechanisms underlying GBS pathogenesis are not fully elucidated. Recent studies have focused on postinfectious molecular mimicry and identified involvement of IgG autoantibodies and innate immune effectors in GBS. Intravenous immunoglobulins (IVIg) and plasma exchange (PE) are two established evidence-based immunomodulatory treatments for GBS, but a significant proportion of GBS patients fails to respond adequately to either therapy. This emphasizes an urgent need for novel and more potent treatments. AREAS COVERED: We discuss novel immunomodulatory therapies presently at different phases of preclinical and clinical investigation. Some drugs in development target pathophysiologic mechanisms such as IgG autoantibody catabolism and complement activation, which are relevant to GBS. EXPERT OPINION: There is an unmet need for more effective immune therapies for GBS. New immunomodulatory therapies under development may provide more potent options for GBS patients who do not respond to IVIg or PE. Future directions may include incorporating neuroprotective interventions based on evolving understanding of mechanisms underlying nerve injury and axonal degeneration.

HDL-based therapeutics: A promising frontier in combating viral and bacterial infections.

Low levels of high-density lipoprotein (HDL) and impaired HDL functionality have been consistently associated with increased susceptibility to infection and its serious consequences. This has been attributed to the critical role of HDL in maintaining cellular lipid homeostasis, which is essential for the proper functioning of immune and structural cells. HDL, a multifunctional particle, exerts pleiotropic effects in host defense against pathogens. It functions as a natural nanoparticle, capable of sequestering and neutralizing potentially harmful substances like bacterial lipopolysaccharides. HDL possesses antiviral activity, preventing viruses from entering or fusing with host cells, thereby halting their replication cycle. Understanding the complex relationship between HDL and the immune system may reveal innovative targets for developing new treatments to combat infectious diseases and improve patient outcomes. This review aims to emphasize the role of HDL in influencing the course of bacterial and viral infections and its and its therapeutic potential.

The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy.

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.

Advances in noncoding RNA in children allergic rhinitis.

BACKGROUND: A chronic condition that significantly reduces a child's quality of life is allergic rhinitis (AR). The environment and allergens that the body is regularly exposed to can cause inflammatory and immunological reactions, which can change the expression of certain genes Epigenetic changes are closely linked to the onset and severity of allergy disorders according to mounting amounts of data. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. METHODS: Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. RESULTS: Recent findings indicate that various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. CONCLUSION: This article demonstrates the significance and progress of ncRNAs in children's AR. The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore.

Immunomodulatory of sesquiterpenoids and sesquiterpenoid dimers-based toll-like receptor 4 (TLR4) from Dysoxylum parasiticum stem bark.

In recent decades, the interest in natural products with immunomodulatory properties has increased due to their therapeutic potential. These products have a wider range of pharmacological activities and demonstrate lower toxicity levels when compared to their synthetic counterparts. Therefore, this study aimed to investigate the immunomodulatory effects of sesquiterpenoids (SQs) and sesquiterpenoid dimers (SQDs) isolated from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark on human and murine cells, particularly focusing on toll-like receptor 4 (TLR4). Utilizing the secreted alkaline phosphatase (SEAP) assay on engineered human and murine TLR4 of HEK-Blue cells, antagonist TLR4 compounds were identified, including SQs 6, 9, and 10, as well as SQDs 17 and 22. The results showed that 10-hydroxyl-15-oxo-α-cadinol (9) had a potent ability to reduce TLR4 activation induced by LPS stimulation, with minimal toxicity observed in both human and murine cells. The SEAP assay also revealed diverse immune regulatory effects for the same ligand. For instance, SQs 12, 14, and 16 transitioned from antagonism on human to murine TLR4. The SQs (4, 7, 11, and 15) and SQDs (18-20) offered partial antagonist effect exclusively on murine TLR4. Furthermore, these selected SQs and SQDs were assessed for their influence on the production of proinflammatory cytokines TNF-α, IL-1α, IL-1ß, and IL-6 of the NF-κB signaling pathway in human and murine macrophage cell lines, showing a dose-dependent manner. Additionally, a brief discussion on the structure-activity relationship was presented.

Dupilumab Therapy Modulates Circulating Inflammatory Mediators in Patients with Prurigo Nodularis.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and skin nodules. Beyond the skin, PN involves circulating blood inflammation that may contribute to systemic disease comorbidities. Dupilumab was recently approved for treatment of PN, but its effects on systemic inflammation are unknown. Thus, we aimed to characterize changes in plasma concentrations of inflammatory proteins after dupilumab treatment. In this exploratory study, plasma samples were collected from 3 patients with moderate-to-severe PN before and after ≥6 months of dupilumab treatment. All patients exhibited clinically significant improvements after treatment. Of the 2569 proteins tested, 186 were differentially expressed after treatment (q < 0.1, fold change > 1.3). Downregulated proteins included cytokines associated with T helper (Th) 1 (IFN-γ, TNF-α), Th2 (IL-4, IL-13), and Th17/Th22 (IL-6, IL-22) signaling. Markers of innate immunity (IL-19, toll-like receptor 1, nitric oxide synthase 2), immune cell migration (CCL20, CD177), and fibrosis (IL-11, IL-22) were also decreased (q < 0.1). Gene set variation analysis of Th2, Th17, and epithelial-mesenchymal transition gene sets showed reduced pathway expression in the post-treatment cohort (P < .05). Plasma cytokine levels of IL-11, nitric oxide synthase 2, IL-13, IL-4, and IFNG (R2 > 0.75, q < 0.10) showed the strongest correlations with pruritus severity. Dupilumab may reduce systemic inflammatory proteins associated with multiple immune and fibrosis pathways in patients with PN, potentially modulating the development of systemic disease comorbidities.

Short- and long-term effects of imatinib in hospitalised COVID-19 patients: A randomised trial.

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients. METHODS: Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients. RESULTS: We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.

Regenerative endodontic therapy: From laboratory bench to clinical practice.

BACKGROUND: Maintaining the vitality and functionality of dental pulp is paramount for tooth integrity, longevity, and homeostasis. Aiming to treat irreversible pulpitis and necrosis, there has been a paradigm shift from conventional root canal treatment towards regenerative endodontic therapy. AIM OF REVIEW: This extensive and multipart review presents crucial laboratory and practical issues related to pulp-dentin complex regeneration aimed towards advancing clinical translation of regenerative endodontic therapy and enhancing human life quality. KEY SCIENTIFIC CONCEPTS OF REVIEW: In this multipart review paper, we first present a panorama of emerging potential tissue engineering strategies for pulp-dentin complex regeneration from cell transplantation and cell homing perspectives, emphasizing the critical regenerative components of stem cells, biomaterials, and conducive microenvironments. Then, this review provides details about current clinically practiced pulp regenerative/reparative approaches, including direct pulp capping and root revascularization, with a specific focus on the remaining hurdles and bright prospects in developing such therapies. Next, special attention was devoted to discussing the innovative biomimetic perspectives opened in establishing functional tissues by employing exosomes and cell aggregates, which will benefit the clinical translation of dental pulp engineering protocols. Finally, we summarize careful consideration that should be given to basic research and clinical applications of regenerative endodontics. In particular, this review article highlights significant challenges associated with residual infection and inflammation and identifies future insightful directions in creating antibacterial and immunomodulatory microenvironments so that clinicians and researchers can comprehensively understand crucial clinical aspects of regenerative endodontic procedures.

Retrospective evaluation of the effect of acid suppressant drugs on leukocyte ratios in dogs with mast cell tumors.

BACKGROUND: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. HYPOTHESIS: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. ANIMALS: Fifty-one dogs with mast cell tumors (MCTs). MATERIALS AND METHODS: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. RESULTS: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417-15 to 5.631; range, 2.654-92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. CONCLUSIONS: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.

Antifungal Plant Defensins as an Alternative Tool to Combat Candidiasis.

Currently, the spread of fungal infections is becoming an urgent problem. Fungi of the Candida genus are opportunistic microorganisms that cause superficial and life-threatening systemic candidiasis in immunocompromised patients. The list of antifungal drugs for the treatment of candidiasis is very limited, while the prevalence of resistant strains is growing rapidly. Therefore, the search for new antimycotics, including those exhibiting immunomodulatory properties, is of great importance. Plenty of natural compounds with antifungal activities may be extremely useful in solving this problem. This review evaluates the features of natural antimicrobial peptides, namely plant defensins as possible prototypes of new anticandidal agents. Plant defensins are important components of the innate immune system, which provides the first line of defense against pathogens. The introduction presents a brief summary regarding pathogenic Candida species, the pathogenesis of candidiasis, and the mechanisms of antimycotic resistance. Then, the structural features of plant defensins, their anticandidal activities, their mechanisms of action on yeast-like fungi, their ability to prevent adhesion and biofilm formation, and their combined action with conventional antimycotics are described. The possible mechanisms of fungal resistance to plant defensins, their cytotoxic activity, and their effectiveness in in vivo experiments are also discussed. In addition, for the first time for plant defensins, knowledge about their immunomodulatory effects is also presented.

Benefits of Mushroom-Based Supplements on Growth Performance, Immunocompetence, and Meat Quality in Poultry.

The restriction on the use of antibiotics in poultry has led to an increase in the use of natural products that could serve as alternatives to antibiotics. Mushrooms contain bioactive compounds that exhibit antifungal, antiparasitic, antibacterial, antioxidant, antiviral, anti-inflammatory, and cytotoxic properties. Hence, they are being tested, revealing as performance-enhancing natural feed additives for livestock. This review focused on the role of different species of mushrooms commonly used in poultry on the performance, immunomodulatory actions, cholesterolemic properties, and meat quality of poultry birds. Different studies reviewed show that mushrooms could positively impact poultry production, improve growth performance, modulate immune response, exert tissue antioxidant activity, influence intestinal morphology, enhance gut microbiome, and improve lipid profile. The variations in their efficacy could be attributed to the variations in physicochemical properties of different species and dosage levels applied in the experiments. However, the use of mushrooms as a natural product supplement is in its infancy, and more basic, pilot and large-scale research is required to make it a viable approach for improving immune responses in the poultry industry.

Neuro-Immunomodulatory Potential of Nanoenabled 4D Bioprinted Microtissue for Cartilage Tissue Engineering.

Cartilage defects trigger post-traumatic inflammation, leading to a catabolic metabolism in chondrocytes and exacerbating cartilage degradation. Current treatments aim to relieve pain but fail to target the inflammatory process underlying osteoarthritis progression. Here, we 4D-bioprint a human cartilage microtissue (HCM) nanoenabled with ibuprofen-loaded poly(lactic-co-glycolic acid) nanoparticles (ibu-PLGA NPs) to locally mitigate inflammation and impair nerve sprouting. Under in vitro inflamed environment, the nanoenabled HCM exhibits chondroprotective potential by decreasing the interleukin (IL)1ß and IL6 release, while sustaining extracellular matrix (ECM) production. In vivo assessments utilizing the air pouch mouse model affirmed the nanoenabled HCM non-immunogenicity. Nanoenabled HCM-derived secretome did not elicit a systemic immune response and decreases locally the recruitment of mature dendritic cells and the secretion of multiple inflammatory mediators and matrix metalloproteinases, when compared to inflamed HCM condition. Notably, the nanoenabled HCM secretome had no impact on the innervation profile of the skin above the pouch cavity, suggesting a potential to impede nerve growth. Overall, HCM nanoenabled with ibu-PLGA NPs emerges as a potent strategy to mitigate inflammation and protect ECM without triggering nerve growth, introducing an innovative and promising approach in the cartilage tissue engineering field. This article is protected by copyright. All rights reserved.

The efficacy of herbal medicines on the length of stay and negative conversion time/rate outcomes in patients with COVID-19: a systematic review.

Introduction: In recent years, diverse initiatives have been carried out to control the COVID-19 pandemic, ranging from measures restricting social activities to analyzing drugs and vaccines. Studies on herbal medicines are also increasingly conducted in various countries as an adjuvant therapy or supplement. Therefore, this systematic review aimed to investigate the efficacy of herbal medicines analyzed from various countries through clinical trials with the randomized controlled trial method. The outcomes of Length of Stay (LOS), Negative Conversion Time (NCT), and Negative Conversion Rate (NCR) were the main focus. Methods: An extensive review of literature spanning from 2019 to 2023 was carried out using well-known databases including PubMed, Scopus, and Cochrane. The search included relevant keywords such as "randomized controlled trial," "COVID-19," and "herbal medicine." Results: A total of 8 articles were part of the inclusion criteria with outcomes of LOS, NCT, and NCR. In terms of LOS outcomes, all types of herbal medicines showed significant results, such as Persian Medicine Herbal (PM Herbal), Persian Barley Water (PBW), Jingyin Granules (JY granules), Reduning Injection, and Phyllanthus emblica (Amla). However, only JY granules showed significant results in NCR outcome, while JY granules and Reduning Injection showed significant results in reducing NCT. Conclusion: These findings enrich our understanding of the potential benefits of herbal medicines in influencing LOS, NCR and NCT parameters in COVID-19 patients. Herbal medicines worked to treat COVID-19 through antiviral, anti-inflammatory, and immunomodulatory mechanisms.

Revisiting the antiangiogenic mechanisms of fluorinated thalidomide derivatives.

Introduction of fluorine into bioactive molecules has attracted much attention in drug development. For example, tetrafluorination of the phthalimide moiety of immunomodulatory drugs (IMiDs) has a strong beneficial effect on the ability to inhibit angiogenesis. The neomorphic activity of E3 ligase complexes is induced by the binding of IMiDs to cereblon. We investigated that a set of eight thalidomide analogs, comprising non- and tetrafluorinated counterparts, did not induce the degradation of neomorphic substrates (IKZF3, GSPT1, CK1α, SALL4). Hence, the antiangiogenic activity of fluorinated IMiDs was not triggered by neosubstrate degradation features. A fluorine scanning of non-traditional IMiDs of the benzamido glutarimide chemotype was performed. By measuring the endothelial cell tube formation, no angiogenesis inhibitors were identified, confirming the narrow structure-activity window of IMiD-induced antiangiogenesis.

Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma.

Immunomodulatory imide drugs (IMiDs) play a crucial role in the treatment landscape across various stages of multiple myeloma. Despite their evident efficacy, some patients may exhibit primary resistance to IMiD therapy, and acquired resistance commonly arises over time leading to inevitable relapse. It is critical to develop novel therapeutic options to add to the treatment arsenal to overcome IMiD resistance. We designed, synthesized, and screened a new class of polyfluorinated thalidomide analogs and investigated their anti-cancer, anti-angiogenic, and anti-inflammatory activity using in vitro and ex vivo biological assays. We identified four lead compounds that exhibit potent anti-myeloma, anti-angiogenic, anti-inflammatory properties using three-dimensional tumor spheroid models, in vitro tube formation, and ex vivo human saphenous vein angiogenesis assays, as well as the THP-1 inflammatory assay. Western blot analyses investigating the expression of proteins downstream of cereblon (CRBN) reveal that Gu1215, our primary lead candidate, exerts its activity through a CRBN-independent mechanism. Our findings demonstrate that the lead compound Gu1215 is a promising candidate for further preclinical development to overcome intrinsic and acquired IMiD resistance in multiple myeloma.

Polysaccharides from a Fermented Beverage Induce Nitric Oxide and Cytokines in Murine Macrophage Cell Line.

Super Ohtaka®, a fermented beverage of plant extracts, is prepared from approximately 50 kinds of fruits and vegetables. Natural fermentation is mainly performed by lactic acid bacteria (Leuconostoc spp.) and yeast (Zygosaccharomyces spp.). Four water-soluble polysaccharide fractions were obtained from Super Ohtaka® by dialysis, ion exchange chromatography, and gel filtration chromatography; these fractions were designated as OEP1-1, OEP1-2, OEP2, and OEP3. OEP1-1 is a polysaccharide composed solely of glucose. The other fractions contained polysaccharides composed of glucose, galactose, mannose, and a small amount of arabinose. OEP2 and OEP3 contained phosphorus, which was not detected in OEP1-1 and OEP1-2. Furthermore, the immunomodulatory activity of the polysaccharides was investigated in murine macrophage cell lines. OEP2 and OEP3 significantly induced nitric oxide (NO) secretion by macrophages in a dose-dependent manner (concentration range of 4 to 100 µg/mL). When the concentration of OEP3 was 100 µg/mL, NO production was almost identical to lipopolysaccharide (LPS; 10 ng/mL) used as a positive control. Notably, OEP3 induced NO secretion more strongly than OEP2. This trend was also observed for TNF-α, IL-1ß, IL-6, and IL-12 p40 secretion. Overall, our in vitro studies on polysaccharides isolated from Super Ohtaka® suggest that the fermented beverage stimulates macrophages and activates the immune system.