Immune Modulatory Effects Research Articles

Enhanced Bioavailability and Immune Benefits of Liposome-Encapsulated Vitamin C: A Combination of the Effects of Ascorbic Acid and Phospholipid Membranes

The bioavailability of vitamin C, or ascorbic acid, depends on limiting transport mechanisms that may be bypassed by liposome-encapsulation. The goal for this study was to evaluate the uptake, antioxidant, and immune-modulating effects of liposome-encapsulated vitamin C (LEC) using Lypo-Spheric® technology, compared to three controls: ascorbic acid (AA), the phospholipid fraction composing the liposome, and placebo. A double-blinded placebo-controlled cross-over study design involved twelve healthy participants attending four clinic visits. At each visit, a baseline blood draw was performed, followed by consumption of 1 g LEC, 1 g AA, the phospholipid component of LEC, or placebo. Additional blood draws were performed at 2, 4, and 6 h. Consuming LEC and AA increased blood levels of vitamin C; the levels were significantly higher after consuming LEC at all timepoints when compared to AA (p < 0.01). LEC consumption increased serum antioxidant capacity (p < 0.01 at 2 h) and protection. Consuming LEC increased IFN-γ levels at 6 h, while consuming the phospholipid fraction rapidly decreased inflammatory cytokines IL-6, MCP-1, and MIP-1α at 2 h. Consuming LEC provided enhanced vitamin C bioavailability and antioxidant protection compared to AA. Consuming the phospholipids had anti-inflammatory effects. The results suggest that LEC provides antioxidant and immune benefits above AA, useful in preventive medicine.

IMMUNOLOGICAL INFLUENCES OF THE CALENDULA OFFICINALIS TEA TREATMENT IN DAIRY COWS

The influence of environmental factors and growth technologies has a substantial impact on health and immunization of animals following antigenic stimulation, so the way vaccine protection is provided cannot be evaluated outside the habitat framework. Medicinal plants have often been used to augment the immune response in humans or animals. In the case of bovine, due to technologies where access to grazing is increasingly available, the animals can benefit directly from the adjuvant influences of medicinal plants in the spontaneous flora. This research aimed at quantifying the effects of orally administered Calendula officinalis aqueous extract (tea) on the innate and adaptive cell-mediated immunity under vaccination conditions, trying to define its immune modulating effect in young bovine. For that, an experiment was performed by administering Calendula officinalis tea perorally to a batch of bovine vaccinated with a complex vaccine for a week post vaccination. On days 0, 7 and 14, in vitro leukocytes blast transformation, and the stress level expressed by the N / L ratio were determined. Vaccination is a stressful event for animals, however, the animals subjected to tea treatment had a higher initial N/L index, which decreased considerably, supporting the decrease in the level of stress by administering marigold tea. The in vitro capacity of the mononuclear cells sampled from the marigold tea treated group was higher towards the standard mitogens PHA M and LPS (p

IMMU-50. IMPACT OF SARS-COV-2 MRNA VACCINES ON PD-L1 EXPRESSION IN INTRACRANIAL TUMORS

Abstract Although immune checkpoint inhibitor (ICI) effectiveness is correlated with intra-tumoral PD-L1 expression, there are no clinically available methods to improve sensitivity to ICIs by modulating PD-L1 expression. mRNA vaccines stimulate robust interferon-dependent innate immune activation leading to four-fold increases in PD-L1 expression on peripheral and intratumoral myeloid cells and enhanced sensitivity to immune checkpoint blockade in preclinical models (Sayour, Grippin, et al., NanoLetters, 2018; Mendez-Gomez, et al., Cell, 2024). We hypothesized that mRNA vaccines targeting SARS-COV-2 would similarly enhance PD-L1 expression in intracranial tumors. To test this hypothesis, we utilized institutional databases to identify 5,524 patients at our institution with pathology reports including the term “PD-L1” from August 2020 to November 2023. Pathological data and dates of SARS-COV-2 vaccination were compiled for each patient. Across the entire cohort (n=5,524), receipt of a SARS-COV-2 mRNA vaccine within 100 days of biopsy was associated with a 55% increase in mean tumor proportion score (TPS) (14% vs 8.9%, p=0.029). In the subset of patients with intracranial tumors (n=187), receipt of a SARS-COV-2 mRNA vaccine within 100 days of biopsy was associated with a massive increase in TPS (57% vs 7.2%, p<0.001). To evaluate the impact of this change on clinical outcomes with immunotherapy, we utilized a second institutional database to assemble a cohort of patients with Stage IV melanoma with intracranial metastasis treated with immune checkpoint blockade during the period August 2020 through November 2023. Patients who received a SARS-COV-2 vaccine within 100 days of initiation of ICI (n=10) exhibited numerically improved overall survival compared to those without SARS-COV-2 mRNA vaccine (n=38) (HR 0.50, 95% CI 0.22-1.2, p=0.06). Median overall survival was 545 days among patients without COVID mRNA vaccination and was not met among those with COVID mRNA vaccination. This data supports further investigation of the immune modulating effect of SARS-COV-2 mRNA vaccines in patients with intracranial tumors treated with immune checkpoint blockade.

Mechanism of the KIAA1429/KLF1/PD-L1 Axis in Regulating Immune Escape in Non-small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC), accounting for approximately 80% of lung cancer cases, remains the leading cause of cancer-related mortality. Immune evasion is a critical challenge in NSCLC, contributing to poor treatment outcomes. This study investigates the role of KIAA1429 in immune evasion, aiming to identify novel therapeutic targets and provide a theoretical basis for NSCLC treatment. NSCLC cell lines were cultured to assess the expression of KIAA1429, KLF transcription factor (KLF1), and programmed cell death ligand 1 (PD-L1). Co-culture experiments were conducted with peripheral blood mononuclear cells (PBMCs) to evaluate cytotoxicity, CD8+T cell proportions, and levels of interferon-gamma (IFN-γ)/interleukin (IL)-10/IL-2. Additionally, N6-methyladenosine (m6A) modification in NSCLC cells, m6A enrichment on KLF1, and KLF1 mRNA stability were analyzed. Results showed increased expression of KIAA1429 and KLF1 in NSCLC cells. Knockdown of KIAA1429 inhibited NSCLC cell proliferation, enhanced PBMC cytotoxicity and CD8+T cell activation, increased IFN-γ and IL-2 levels, and decreased IL-10 levels. Mechanistically, KIAA1429 stabilized KLF1 mRNA level through m6A modification, promoting both KLF1 and PD-L1 expression. Overexpression of KLF1 or PD-L1 reversed the immune-modulating effects of KIAA1429 knockdown. In conclusion, KIAA1429 facilitates immune evasion in NSCLC by stabilizing KLF1 mRNA and upregulating PD-L1 expression.

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

Growth, development and commercial traits of sturgeon fish species under industrial fi sh farming conditions when use the feed additive Abiotonic

Artificial fish farming including commercial sturgeon farming using highly nutritious balanced feeds is nothing less than a strategically important area in Russian agriculture. In recent years, methods for increasing animal productivity using highly biologically active additives both natural and artifi cial, which have a growth-stimulating, protective and immune-modulating eff ect on the body of animals at various stages of development, have found wide application. These include the feed additive Abiotonic. In the literature studied by us, we found no information on the eff ect of the feed additive Abiotonic on the growth, development and livability of sturgeon fi sh, as well as on the quality indicators of the resulting fi sh products. In this regard, studies aimed at studying the eff ect of the vitamin-microelement growth immunostimulant Abiotonic on the productivity of sturgeon fi sh are relevant. The purpose of the research was to study the growth, development and commercial traits of sturgeon fi sh species under industrial fi sh farming conditions using the feed additive Abiotonic. The research established the optimal amount of the feed additive Abiotonic for use in the diets of the hybrid Russian and Siberian sturgeon inder industrial fi sh farming conditions. Thus, when rearing sturgeon fi sh with high productive and commercial traits, as well as with low feed costs per unit of fi sh weight gain and the cost of fi sh products under industrial conditions, we recommend that fish farms use the feed additive Abiotonic in the diets of sturgeon fi sh in the mount of 1.0 ml per 1.0 kg of fi sh body weight.

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.

Clinical and experimental investigations into the immune modulatory effects of Qianjinba polysaccharides on a rheumatoid arthritis mouse model: in vivo and in vitro studies

Clinical and experimental investigations into the immune modulatory effects of Qianjinba polysaccharides on a rheumatoid arthritis mouse model: in vivo and in vitro studies

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.

HUMIC ACIDS: PROPERTIES, STRUCTURE, AND APPLICATION

Humic substances (HSs) are a diverse class of natural compounds with no fixed chemical composition, formed from plant and microbial residues through the action of environmental factors and living organisms over many years. Despite extensive research spanning two centuries, the complex and variable nature of HSs' structure remains a subject of scientific inquiry. These substances, notably humic acids, fulvic acids, and humin, play crucial roles in ecological and environmental processes due to their abundant functional groups and resilience to biodegradation. This review explores the intricate structure and properties of HSs, their classification, and their occurrence in nature. It highlights the different models proposed to describe the structural fragments of humic acids, emphasizing their aromatic cores and diverse functional groups. The variability in the molecular weight distribution of HSs, attributed to their polydisperse nature, is also discussed, along with methods used for their determination, such as exclusion chromatography. Furthermore, the elemental and functional compositions of humic acids are examined, detailing their acid-base properties and capacity for heavy metal complexation. The synthesis of HSs from natural sources, such as soil, peat, coal, and artificial processes, is covered, showcasing methods like alkaline extraction and hydrothermal treatment. Recent advancements in artificial humification, including oxidative ammonolysis and Fenton reagent-based oxidation, are reviewed for their potential in producing environmentally friendly humic materials from lignin and waste biomass. The study concludes by underscoring the environmental significance and practical applications of HSs, particularly in agriculture, soil conditioning, and environmental remediation. The diverse properties and synthesis methods of HSs make them promising candidates for sustainable material production and environmental management. Humic acids are versatile compounds beneficial for human health due to their potent antioxidant properties, immune-modulating effects, and support for gastrointestinal health and detoxification. Structurally diverse, they feature groups like carboxyl, phenolic hydroxyl, quinones, ketonic carbonyls, amino, and sulfhydryl, contributing to their stability and amphiphilic nature. In pharmaceutical applications, they show promise for drug delivery, antioxidant therapies, wound healing, antimicrobial actions, and biofilm disruption, underlining their biocompatibility and safety. Key words:

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.