Immune Modulatory Effects Research Articles

Influence of blood pressure targets on inflammation and associations between inflammatory markers and vasopressor usage after cardiac arrest - a substudy of a randomized clinical trial

Abstract Background Following resuscitation from cardiac arrest, a profound systemic inflammatory response may develop. In observational studies of critically ill patients an association between levels of inflammation and vasopressor usage has been found. Higher levels of inflammation may lead to higher vasopressor needs due to vasoplegia and cardiac dysfunction, however, catecholamines, including vasopressors also have immune modulatory effects. In the Blood Pressure and Oxygenation Targets in Post resuscitation Care (BOX) trial patients were randomized to a high or low blood pressure target, and vasopressor usage was increased in the high blood pressure target group. Therefore, the inflammatory response evoked by cardiac arrest, may have been altered by differences in vasopressor usage according to blood pressure target in this trial. Purpose To determine if differences in vasopressor and inotropy usage associated with randomization to a high compared to a low blood pressure target affects the inflammatory response after OHCA, and to investigate the association between inflammation and vasopressor and inotropy usage. Methods In the BOX trial, comatose OHCA patients with a presumed cardiac etiology were randomized to a blinded intervention of either a high (77mmHg) or a low blood pressure target (63mmHg). The inflammatory markers of leukocytes and CRP were measured at 0, 24, 48, and 72 hours. The average Vasoactive-Inotropic Score (VIS) was determined during initial 72 hours. The associations between average CRP, leukocytes, and VIS during initial 72 hours were determined by Spearman’s correlation analysis. Results The BOX trial included 789 resuscitated comatose OHCA patients, and 788 patients had at least 1 measurement of leukocytes and CRP. The median age was 64 (IQR 54-73), females constituted 19%, 1 year mortality was 36%. There was no difference in leukocytes and CRP at admission between the high and low blood pressure target groups (Figure 1). Leukocytes were slightly higher at 24 hours (p<0.01) in the high blood pressure target group, but no group differences were found at 48 and 72 hours, and CRP levels did not differ at 24, 48, or 72 hours. The average VIS was 19 (11-32) and 11 (5-19), p<0.01, in the two groups, with VIS being consistently higher at all timepoints beyond ICU admission (all p<0.01, data not shown) in patients with a high blood pressure target. Both average CRP and leukocytes were weakly correlated with average VIS at 0-72 hours for both blood pressure targets, r=0.17 and r=0.20, respectively for a high target (both p<0.01), and r=0.17 and r=0.20, respectively for a low target (both p<0.01). Conclusions In conclusion, increased vasopressor and inotropy usage in this randomized, blinded study of blood pressure targets after OHCA, did not lead to clinically relevant changes in inflammation. Inflammatory markers and VIS were correlated to a similar degree for both blood pressure targets.Figure 1, LeukocytesFigure 2, CRP

Some Applications of Hericium erinaceus Mushrooms: A Review

The Lion's Mane mushroom, which has the scientific name Hericium erinaceus, can be defined as a medicinal fungus type. For very long time, it has been utilized in the conventional medicine in Asia for a variety of purposes. In the past few years, there had been a great deal of interest directed towards potential benefits to the health, which could be provided by this unique type of mushroom in particular, when it comes to the treatment of various diseases. The concentration will be focused on examining the way that Hericium erinaceus as well as its bioactive elements could be utilized for therapeutic purposes within the area od disease control. This review states the possible Hericium erinaceus advantages in cases that are related to some health issues, such as metabolic problems, gastrointestinal diseases, neurodegenerative disorders, and immune system problems. In addition to that, the present paper discusses the work that is used for providing the therapeutic effects. It is stated that some of the characteristics of the Hericium erinaceus include having anti-inflammatory, neuro-protective, anti-oxidant, and immune-modulatory effects. Even though more studies are needed for detailed understanding of all the mechanisms that are involved in its activities, presenting evidences that strongly suggest possible Hericium erinaceus uses as one of the natural cures for a variety of illnesses, it is known as well in some cases as lion's mane mushroom, which fungus type that comes with extensive history and many potential advantages. As a result of its distinctive morphology, including bio-active compounds, in addition to its conventional uses have combined to the generation of much interest in a variety of areas. More research is needed for full understanding of the way that it works for the therapeutic applications and its potential implementations in the area of nutrition, cooking, and medicine. The cultivation of Hericium erinaceus might be viewed as an activity of conservation and business production.

Immune Implications of Cholesterol-Containing Lipid Nanoparticles.

The majority of clinically approved nanoparticle-mediated therapeutics are lipid nanoparticles (LNPs), and most of these LNPs are liposomes containing cholesterol. LNP formulations significantly alter the drug pharmacokinetics (PK) due to the propensity of nanoparticles for uptake by macrophages. In addition to readily engulfing LNPs, the high expression of cholesterol hydroxylases and reactive oxygen species (ROS) in macrophages suggests that they will readily produce oxysterols from LNP-associated cholesterol. Oxysterols are a heterogeneous group of cholesterol oxidation products that have potent immune modulatory effects. Oxysterols are implicated in the pathogenesis of atherosclerosis and certain malignancies; they have also been found in commercial liposome preparations. Yet, the in vivo metabolic fate of LNP-associated cholesterol remains unclear. We review herein the mechanisms of cellular uptake, trafficking, metabolism, and immune modulation of endogenous nanometer-sized cholesterol particles (i.e., lipoproteins) that are also relevant for cholesterol-containing nanoparticles. We believe that it would be imperative to better understand the in vivo metabolic fate of LNP-associated cholesterol and the immune implications for LNP-therapeutics. We highlight critical knowledge gaps that we believe need to be addressed in order to develop safer and more efficacious lipid nanoparticle delivery systems.

Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles

Background: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as an alternative to live-cell administration for Acute Respiratory Distress Syndrome (ARDS). MSC-EVs can be chiefly influenced by the environment to which the MSCs are exposed. Here, lipopolysaccharide (LPS) priming of MSCs was used as a strategy to boost the natural therapeutic potential of the EVs in acute lung injury (ALI). Methods: The regenerative and immunemodulatory effect of LPS-primed MSC-EVs (LPS-EVs) and non-primed MSC-EVs (C-EVs) were evaluated in vitro on alveolar epithelial cells and macrophage-like THP-1 cells. In vivo, ALI was induced in adult male rats by the intrapulmonary instillation of HCl and LPS. Rats (n = 8 to 22/group) were randomized to receive a single bolus (1 × 108 particles) of LPS-EVs, C-EVs, or saline. Lung injury severity was assessed at 72 h in lung tissue and bronchoalveolar lavage. Results: In vitro, LPS-EVs improved wound regeneration and attenuated the inflammatory response triggered by the P. aeruginosa infection, enhancing the M2 macrophage phenotype. In in vivo studies, LPS-EVs, but not C-EVs, significantly decreased the neutrophilic infiltration and myeloperoxidase (MPO) activity in lung tissue. Alveolar macrophages from LPS-EVs-treated animals exhibited a reduced expression of CXCL-1, a key neutrophil chemoattractant. However, both C-EVs and LPS-EVs reduced alveolar epithelial and endothelial permeability, mitigating lung damage. Conclusions: EVs from LPS-primed MSCs resulted in a better resolution of ALI, achieving a greater balance in neutrophil infiltration and activation, while avoiding the complete disruption of the alveolar barrier. This opens new avenues, paving the way for the clinical implementation of cell-based therapies.

Immune modulatory effects of tulathromycin, gamithromycin, and oxytetracycline in cattle

Certain classes of antibiotics, including tetracyclines and macrolides, are known to exert immune suppressive effects in other species but the immune modulatory effects of these antibiotics have not been previously studied in cattle. To address this question, we investigated the effects of oxytetracycline, gamithromycin, and tulathromycin on T cell and macrophage responses to activation, using in vitro assays. In addition, we assessed the impact of these antibiotics on T cell responses in vivo following treatment of healthy cattle with currently recommended doses of each of the three antibiotics. We found that all 3 antibiotics markedly suppressed T cell proliferation in vitro at relevant therapeutic drug concentrations and significantly suppressed macrophage activation responses to LPS. In cattle treated with a single dose of each antibiotic, we observed significant suppression of T cell proliferation and cytokine production beginning as early as 6 h after administration, with increasing immune suppression observed at 48 h. Taken together, these results indicate that commonly used antibiotics in cattle exert significant immune modulatory activity, in addition to their antimicrobial activity. These off-target effects should be considered when using antibiotics for prophylaxis or metaphylaxis in high-risk dairy or beef cattle (192 words).

Staphylococcus aureus SaeRS impairs macrophage immune functions through bacterial clumps formation in the early stage of infection

The Staphylococcus aureus (S. aureus) SaeRS two-component system (TCS) regulates over 20 virulence factors. While its impact on chronic infection has been thoroughly discussed, its role in the early stage of infection remains elusive. Since macrophages serve as the primary immune defenders at the onset of infection, this study investigates the influence of SaeRS on macrophage functions and elucidates the underlying mechanisms. Macrophage expression of inflammatory and chemotactic factors, phagocytosis, and bactericidal activity against S. aureus were assessed, along with the evaluation of cellular oxidative stress. SaeRS was found to impair macrophage function. Mechanistically, SaeRS inhibited NF-κB pathway activation via toll-like receptor 2 (TLR2). Its immune-modulating effect could partially be explained by the strengthened biofilm formation. More importantly, we found SaeRS compromised macrophage immune functions at early infection stages even prior to biofilm formation. These early immune evasion effects were dependent on bacterial clumping as cytokine secretion, phagocytosis, and bactericidal activity were repaired when clumping was inhibited. We speculate that the bacterial clumping-mediated antigen mask is responsible for SaeRS-mediated immune evasion at the early infection stage. In vivo, ΔsaeRS infection was cleared earlier, accompanied by early pro-inflammatory cytokines production, and increased tissue oxidative stress. Subsequently, macrophages transitioned to an anti-inflammatory state, thereby promoting tissue repair. In summary, our findings underscore the critical role of the SaeRS TCS in S. aureus pathogenicity, particularly during early infection, which is likely initiated by SaeRS-mediated bacterial clumping.

Corticosteroid-induced bradycardia following high-dose methylprednisolone administration: a case report

Introduction: Besides their wide use in the clinical field due to their anti-inflammatory and immune-modulating effect, corticosteroids still have a lot of adverse effects. The most common adverse effects are hyperglycemia, hypertension, osteoporosis, psychosis, immunosuppression, weight gain, and hyperlipidemia. Another important side effect is cardiac arrhythmias. Case presentation: We report a case of a 43-year-old woman with multiple sclerosis who developed symptomatic bradycardia after 3 days of treatment with a high dose of methylprednisolone. The patient received a dose of atropine and her bradycardia resolved after 36 h of stopping methylprednisolone. Discussion: While tachyarrhythmias are more common, bradyarrhythmias such as bradycardia and premature atrial or ventricular contraction are rare but crucial to be considered. Conclusion: Corticosteroid-induced bradycardia is usually in sinus rhythm and has an unknown etiology, possibly occurring at high and low doses. The majority of cases in the literature were asymptomatic and resolved spontaneously.

Preconditioning with Ginsenoside Rg3 mitigates cardiac injury induced by high-altitude hypobaric hypoxia exposure in mice by suppressing ferroptosis through inhibition of the RhoA/ROCK signaling pathway

Ethnopharmacological relevanceGinseng has historically been utilized as a conventional herbal remedy and dietary supplement to enhance physical stamina and alleviate fatigue. The primary active component of Ginseng, Ginsenoside Rg3 (GS-Rg3), possesses diverse pharmacological properties including immune modulation and anti-inflammatory effects. Furthermore, GS-Rg3 has demonstrated efficacy in mitigating tissue and organ damage associated with metabolic disorders such as hypertension, hyperglycemia, and hyperlipidemia. Nevertheless, its potential impact on high-altitude cardiac injury (HACI) remains insufficiently explored. Aim of the studyThe aim of this study was to examine the potential cardioprotective effects of Ginsenoside Rg3, and to investigate how Ginsenoside Rg3 preconditioning can enhance high-altitude cardiac injury by inhibiting the RhoA/ROCK pathway and ferroptosis in cardiac tissue. The findings of this study may contribute to the development of novel therapeutic strategies using traditional Chinese medicine for high-altitude cardiac injury, based on experimental evidence. Materials and methodsA hypobaric hypoxia chamber was employed to simulate hypobaric hypoxia conditions equivalent to an altitude of 6000 m. Through a randomization process, groups of six male mice were assigned to receive either saline, Ginsenoside Rg3 at doses of 15 mg/kg or 30 mg/kg, or lysophosphatidic acid (LPA) at 1 mg/kg. The impact of Ginsenoside Rg3 on high altitude-induced arrhythmias was evaluated using electrocardiography. Cardiac pathology sections stained with hematoxylin and eosin were evaluated for damage, with the extent of cardiomyocyte damage observed via transmission electron microscopy. The impact of Ginsenoside Rg3 on high-altitude cardiac injury was investigated through analysis of serum biomarkers for cardiac injury (CK-MB, BNP), inflammatory cytokines (TNF, IL-6, IL-1β), reactive oxygen species (ROS) and glutathione (GSH). The expression levels of hypoxia and hypoxia-related proteins in myocardial tissues from each experimental group were assessed using Western blot analysis. Following a review of the existing literature, the traditional regulatory mechanisms of ferroptosis were examined. Immunofluorescence staining of cardiac tissues and Western blotting techniques were utilized to investigate the impact of Ginsenoside Rg3 on cardiomyocyte ferroptosis through the RhoA/ROCK signaling pathway under conditions of hypobaric hypoxia exposure. ResultsPre-treatment with Ginsenoside Rg3 improved high altitude-induced arrhythmias, reduced cardiomyocyte damage, decreased cardiac injury biomarkers and inflammatory cytokines, and lowered the expression of hypoxia-related proteins in myocardial tissues. Both Western blotting and immunofluorescence staining of cardiac tissues demonstrated that exposure to high-altitude hypobaric hypoxia results in elevated expression of ferroptosis and proteins related to the RhoA/ROCK pathway. Experimental validation corroborated that the role of the RhoA/ROCK signaling pathway in mediating ferroptosis. ConclusionsThe findings of our study suggest that preconditioning with Ginsenoside Rg3 may attenuate cardiac injury caused by high-altitude hypobaric hypoxia exposure in mice by inhibiting ferroptosis through the suppression of the RhoA/ROCK signaling pathway. These findings contribute to the current knowledge of Ginsenoside Rg3 and high-altitude cardiac injury, suggesting that Ginsenoside Rg3 shows potential as a therapeutic agent for high-altitude cardiac injury.

Production, analysis, and safety assessment of a soil and plant-based natural material with microbiome- and immune-modulatory effects

It has been suggested that reduced contact with microbiota from the natural environment contributes to the rising incidence of immune-mediated inflammatory disorders (IMIDs) in western, highly urbanized societies. In line with this, we have previously shown that exposure to environmental microbiota in the form of a blend comprising of soil and plant-based material (biodiversity blend; BDB) enhances the diversity of human commensal microbiota and promotes immunoregulation that may be associated with a reduced risk for IMIDs. To provide a framework for future preclinical studies and clinical trials, this study describes how the preparation of BDB was standardized, its microbial content analysed and safety assessments performed. Multiple batches of BDB were manufactured and microbial composition analysed using 16S rRNA gene sequencing. We observed a consistently high alpha diversity and relative abundance of bacteria normally found in soil and vegetation. We also found that inactivation of BDB by autoclaving effectively inactivates human and murine bacteria, viruses and parasites. Finally, we demonstrate that experimental mice prone to develop IMIDs (non-obese diabetic, NOD, mouse model) can be exposed to BDB without causing adverse effects on animal health and welfare. Our study provides insights into a potentially safe, sustainable, and cost-effective approach for simulating exposure to natural microbiota, which could have substantial impacts on health and socio-economic factors.

Mitigating the Impact of HIV on Organ Function: Blood Transfusions as a Therapeutic Strategy

HIV (Human Immunodeficiency Virus) significantly impacts organ function, leading to various complications that can adversely affect the health and quality of life of individuals living with the virus. This review explores the multifaceted effects of HIV on organ systems, including the cardiovascular, renal, hepatic, and pulmonary functions, and highlights the potential of blood transfusions as a therapeutic strategy to mitigate these adverse effects. Blood transfusions can effectively address anemia—a common complication in HIV-positive individuals—enhancing oxygen delivery to tissues and improving overall organ function. Additionally, blood transfusions may exert immune-modulating effects, contributing to improved immune responses and potentially reducing the risk of opportunistic infections. This review discusses clinical evidence supporting the benefits of blood transfusions in enhancing organ function and quality of life among HIV-positive patients. Furthermore, it addresses the challenges and considerations associated with transfusion therapy, emphasizing the importance of individualized patient assessments and coordinated care strategies. Keywords: anemia, blood transfusions, HIV, immune response, organ function

Immune and microbiome modulatory effects of Limosilactobacillus fermentum NCDC 400 in an immunocompromised mouse model

The present study was aimed to assess and validate the safety and functional efficacy of an indigenous probiotic strain Limosilactobacillus fermentum NCDC 400 (hereafter, LFN400) in an immunocompromised murine model. The study included four groups; a normal control (NC) group without immune suppression; an experimental model control (MC) with immune suppression induced via intraperitoneal cyclophosphamide (Cy) administration; and two MC groups orally administered with either low dose (LD) or high dose (HD) of LFN400 at dose 108 and 1010 CFU/mouse/day, respectively, for 15-days. Both control groups received normal saline as placebo control. LFN400 improved specific experimental characteristics including hematological and serum biochemical markers. Compared to MC group, LFN400-fed groups showed markedly (P < 0.05) decreased arrays of detrimental caecal enzymes. We did not observe instances of bacterial translocation of LFN400 from gut to bloodstream or extra-intestinal organs. LFN400 intake significantly (P < 0.05) enhanced spleen cell differentiation, immune and oxidative stress markers, and restored Cy-induced histopathological changes in multiple tissues, including the spleen. There was no genotoxic effect of LFN400 on bone marrow cells. Although not statistically significant, LFN400 feeding moderately increased gut microbiome diversity, supporting the growth of beneficial saccharolytic microorganisms and reducing the presence of pathobionts. The findings demonstrate that the probiotic strain LFN400 possesses in vivo safety and immunomodulatory potency and thus should be considered a potential candidate for future human clinical studies.

Lactoferrin: A Promising Therapeutic Molecule against Human Papillomavirus.

Lactoferrin is a multifunctional glycoprotein naturally found in mammalian secretions, predominantly in colostrum and milk. As a key component of dairy foods, lactoferrin enhances viral protection and boosts human health, owing to its fundamental properties including antiviral, anti-inflammatory, and immune-modulatory effects. Importantly, the antiviral effect of lactoferrin has been shown against a range of viruses causing serious infections and threatening human health. One of the viruses that lactoferrin exerts significant antiviral effects on is the human papillomavirus (HPV), which is the most prevalent transmitted infection affecting a myriad of people around the world. Lactoferrin has a high potential to inhibit HPV via different mechanisms, including direct binding to viral envelope proteins or their cell receptors, thereby hindering viral entry and immune stimulation by triggering the release of some immune-related molecules through the body, such as lymphocytes. Along with HPV, lactoferrin also can inhibit a range of viruses including coronaviruses and hepatitis viruses in the same manner. Here, we overview the current knowledge of lactoferrin and its effects on HPV and other viral infections.

The alleviative effects of canagliflozin on imiquimod-induced mouse model of psoriasis-like inflammation.

Psoriasis is a life-long immune-mediated dermatosis with thickened, reddish, and flaky skin patches. Canagliflozin is a gliflozin antidiabetic with non-classical remarkable antioxidative, anti-inflammatory, anti-proliferative, and immune-modulating effects. The aim of this study is to examine the probable effects of topical canagliflozin on a mouse model of imiquimod-provoked psoriasis-like dermatitis. The study evaluated 20 Swiss white mice, sorted haphazardly into 4 groups of 5 animals each. Every mouse, with the exception of the control group, had imiquimod applied topically to their shaved backs for 7 days. The control group included healthy mice that were not given any treatment. Mice in the other three groups underwent topical treatment with vehicle (induction group), 0.05% clobetasol propionate ointment (clobetasol group), or 4% canagliflozin emulgel (canagliflozin 4% group) on exactly the same day as imiquimod cream was administered. Topical canagliflozin markedly lowered the intensity of imiquimod-provoked psoriasis eruptions, featuring redness, glossy-white scales, and acanthosis, while also correcting histopathological aberrations. Canagliflozin administration to imiquimod-exposed animals resulted in significantly decreased cutaneous concentrations of inflammatory mediators such as IL-8, IL-17, IL-23, and TNF-α, with raised levels of IL-10. Canagliflozin further lowered proliferative factors involving Ki-67 and PCNA, diminished oxidative indicators such as MDA and MPO, and augmented the activity of antioxidant markers, notably SOD and CAT. Canagliflozin might alleviate the imiquimod-induced animal model of psoriasis, probably thanks to its profound anti-inflammatory, antioxidant, antiangiogenic, and antiproliferative activities.

Flavonoid intakes, chronic obstructive pulmonary disease, adult asthma, and lung function: a cohort study in the UK Biobank

BackgroundGiven their antioxidative stress, anti-allergic, anti-inflammatory, and immune-modulating effects, flavonoids are hypothesized to play a role in preventing chronic obstructive pulmonary disease (COPD) and asthma. ObjectivesThis cohort study aimed to examine associations between flavonoid intake and COPD, asthma, and lung function. MethodsAmong 119,466 participants of the UK Biobank, median [interquartile range] age of 60 [53, 65] y, we estimated intakes of flavonoids, flavonoid-rich foods, and a flavodiet score from 24-h diet assessments. Prospective associations with both incident COPD and asthma and cross-sectional associations with measures of lung function [%predicted forced expiratory volume in 1s (FEV1); and FEV1/forced vital capacity (FVC)] were examined using multivariable-adjusted Cox proportional hazards and linear regression models, respectively. We investigated mediation by inflammation––represented by the INFLA score––and stratified analyses by smoking status. ResultsCompared with low intakes, moderate intakes of total flavonoids, flavonols, theaflavins + thearubigins, and flavanones, and moderate-to-high intakes of flavanol monomers, proanthocyanidins, anthocyanins, flavones, and the flavodiet score were associated with up to an 18% lower risk of incident COPD {e.g., [hazard ratio (95% confidence interval) for total flavonoids: 0.83 (0.75, 0.92)]} but not incident asthma. Furthermore, compared with low intakes, higher intakes of all flavonoid subclasses (except theaflavins + thearubigins), and the flavodiet score were associated with better percent predicted FEV1 baseline. Associations were most apparent in ever (current or former) smokers. Flavonoid intakes were inversely associated with the INFLA score, which appeared to mediate 11%–14% of the association between intakes of proanthocyanidins and flavones and incident COPD. ConclusionsModerate-to-high flavonoid intakes were associated with a lower risk of COPD and better lung function, particularly among ever smokers. Promoting intakes of healthy flavonoid-rich foods, namely, tea, apples, and berries, may improve respiratory health and lower COPD risk, particularly in individuals with a smoking history.

Comprehensive analysis of secretome and transcriptome stability of Wharton jelly mesenchymal stromal cells during good manufacturing practice-compliant production

BackgroundMesenchymal stromal cells (MSCs) hold promise for cell-based therapies due to their ability to stimulate tissue repair and modulate immune responses. Umbilical cord-derived MSCs from Wharton jelly (WJ) offer advantages such as low immunogenicity and potent immune modulatory effects. However, ensuring consistent quality and safety throughout their manufacturing process remains critical. RNA sequencing (RNA-seq) emerges as a crucial tool for assessing genetic stability and expression dynamics in cell-based therapeutic products. MethodsWe examined the secretome and transcriptome of WJ-MSC signatures throughout Good Manufacturing Practice (GMP) production, focusing on the performance of total RNA or Massive Analysis of cDNA Ends (MACE) sequencing. ResultsThrough extensive transcriptomic analysis, we demonstrated consistent stability of WJ-MSC expression signatures across different manufacturing stages. Notably, MACE-seq showed improved identification of key expression patterns related to senescence and immunomodulation. ConclusionsThese findings highlight the potential of MACE-seq as a quality assessment tool for WJ-MSC-based therapies, ensuring their efficacy and safety in clinical applications. Importantly, MACE-seq demonstrated its value in characterizing WJ-MSC-derived products, offering insights that traditional assays cannot provide.

A fructan-type garlic polysaccharide upregulates immune responses in macrophage cells and in immunosuppressive mice

The anti-inflammatory effects of plant polysaccharides are well known. However, the stimulatory effects of polysaccharides under immunosuppressive conditions and their link with the polysaccharide structure is underexplored. In this work, the immune modulatory effects of a garlic polysaccharide (GP) are investigated via in vitro and vivo methods. It is observed that GP enhance the immune response of macrophages (RAW264.7) as indicated by the elevated levels of nitric oxide, TNF-α and IL-6. The observation that GP are able to stimulate the immune response in vitro was then explored with the use of an immunosuppressed mouse model. Surprisingly, GP exhibited dose-dependent up-regulatory impacts on the cyclophosphamide (CTX) suppressed levels of cytokines such as IFN-γ and IL-6 and immunoglobulins (e.g. IgA and IgG). The GP intervention reversed histopathological damage to the small intestine and spleen and increased fecal short-chain fatty acid levels. Moreover, GP modulates the gut microbiota dysbiosis by increasing the abundance of immunogenic bacteria such as g__norank_f__Erysipelotrichaceae, while inhibiting the over-abundance of g_Bacteroides. Functional predictions indicated that gut biomarkers of GP possessed the functions of glycoside hydrolase family 32 (GH32) and β-fructofuranosidase. It is concluded that GP is a promising immunostimulant for immune-compromised individuals.

Does the use of statins alter the risk of rheumatoid arthritis? A systematic review and meta-analysis.

Statins have anti-inflammatory and immune-modulatory effects which could alter the risk of rheumatoid arthritis (RA). We reviewed published literature and conducted a meta-analysis to examine if statins have an impact on the risk of RA. Case-control studies, cohort studies, or randomized controlled trials (RCT) published on the PubMed, Scopus, and EMBASE databases up to 30th October 2023 were searched. The association between statin use and risk of RA was pooled in a random-effects meta-analysis. Nine studies (four cohort, four case-control, and one RCT) were included. Overall, the analysis failed to note an association between the use of statins and the risk of RA with the pooled OR being 0.93 (95% CI 0.82, 1.06). High heterogeneity was noted with I2 = 75%. Results were consistent across study types with no association noted between prior statin use and risk of RA in case-control studies (OR: 0.88 95% CI: 0.69, 1.13), cohort studies (OR: 1.01 95% CI: 0.92, 1.10), and the lone RCT (OR: 1.40 95% CI: 0.50, 3.92). Current literature shows that there is no association between the use of statins and the risk of RA. Further rigorous studies taking into account patient factors, duration of statin exposure, and other confounders are needed to generate better evidence.

Investigating the anti-inflammatory and immune-modulatory effects of “Gola” guava fruit and leaf extract in alleviating papain-induced knee osteoarthritis

IntroductionThis present research was designed to investigate the anti-inflammatory and immune-modulatory effects of a 50% hydroethanolic extract of “Gola” guava fruit (GF50%) and guava leaf (GL50%) against papain-induced knee osteoarthritis (KOA).MethodsSixty Sprague–Dawley rats were divided into five groups (10 rats/ group): T0 (negative control), T1 (positive control), T2 (200 mg/kg GF50%), T3 (400 mg/kg GF50%), T4 (200 mg/kg GL50%), and T5 (400 mg/kg GL50%). Physical parameters were evaluated throughout the trial, while biochemical, histopathological, and radiographic analyses were performed at 0, 15, and 30 days. The histopathological and radiographic analyses were evaluated using the Osteoarthritis Research Society International (OARSI) score and Kellgren–Lawrence (KL) classification systems, respectively.Results and discussionThe T1 group demonstrated a significant increase in knee diameter, confirming successful OA induction. The T5 group maintained a significantly lower body weight at day 30, and the T3 group exhibited the highest weight gain. The high dose of GL50% (400 mg/ kg) effectively reduced knee inflammation and significantly downregulated myeloperoxidase (MPO), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In contrast, it significantly (p &amp;lt; 0.001) upregulated the serum and knee capsule tissue superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In addition, histopathological and X-ray examinations also confirmed the chondroprotective potential of GL50% extract against OA. Consequently, 400 mg/kg GL50% exhibited anti-inflammatory and chondroprotective potential by lowering oxidative stress and pro-inflammatory cytokines and elevating antioxidant status. These findings could provide a theoretical basis for understanding the mechanism and potential medicinal value of guava fruit and leaf in treating KOA.

Navigating the Cow’s Milk Allergy Journey: From Diagnosis to Nutritional Optimisation

Cow’s milk allergy (CMA) currently ranks as one of the most common infant food allergies and requires timely diagnosis and appropriate management to mitigate the impact on growth and developmental outcomes and minimise patient/parent distress. During this symposium, chaired by Yvan Vandenplas, Emeritus at KidZ Health Castle, University Hospital Brussels, Belgium, leading experts in paediatric gastroenterology, allergy, and nutrition, discussed how best to navigate the CMA journey in clinical practice, from accurate differential diagnosis to nutritional optimisation. Annamaria Staiano, Professor of Paediatrics and Chief of the Department of Translational Medical Sciences at the University of Naples ‘Federico II’, Italy, discussed the complexities of differentiating disorders of gut–brain interaction (DGBI), previously known as functional gastrointestinal disorders, from CMA, and considered the potential role of the Cow’s Milk Related Symptom Score (CoMiSSTM) in ensuring infants follow the correct diagnostic pathway. Ralf Heine, Paediatric Gastroenterologist, Allergist, and Honorary Research Fellow at the Murdoch Children’s Research Institute in Melbourne, Australia, explored the immune-modulating effects of human milk oligosaccharides (HMO) and lactose on the gastrointestinal (GI) microbiota in infants, highlighting the importance of the early-life microbiome during the nutritional management of CMA. Rosan Meyer, Paediatric Dietitian and visiting Professor at both KU Leuven, Belgium, and the University of Winchester, UK, focused on the final phase of CMA management, the reintroduction of cow’s milk protein, and also examined new evidence to support the optimal timing and strategy for this key step in clinical practice.

Extraction and molecular characterisation of polysaccharides from Suaeda maritima for their immunomodulatory effects

In the present study, Suaeda maritima polysaccharides (SMPs) were identified, characterised and evaluated for their immune-modulating effects on RAW264.7 macrophages and the underlying biological processes. Two acidic polysaccharides (SMP-F1 and SMP-F2) were obtained via ion-exchange chromatography from the crude polysaccharide (SMP-C). The SMP-C and its fractions mainly contained carbohydrates, proteins and sulphates, in variable proportions. Glucose, mannose, galactose and arabinose were the primary monosaccharide units, accompanied by smaller amounts of rhamnose and xylose. The molecular weight (Mw) of the SMPs ranged from 76.2 × 103 to 245.0 × 103 g/mol. SMPs can significantly induce the production of NO by up-regulating iNOS expression. The results showed that SMPs could increase TNF-α, IL-6, IL-10 and IL-12 expression. In addition, SMP-F2 significantly boosts inflammatory reactions more than SMP-C or SMP-F1. Further study revealed that SMP-F2 was found to stimulate macrophage phagocytosis and the expression of CD11b, CD14, CD40 and TLR4. The major chains of the strongest immunostimulant, SMP-F2, were mainly 1,3-linked Manp, 1,4-linked Glcp and 1,4-linked Galp. The side chain of SMP-F2 was 1,3,6-linked Manp and 1,4,6-linked Galp, with terminals of arabinose, mannose and glucose. These findings show that SMPs, particularly SMP-F2, promote the ability to modulate immunological responses.