Immunomodulatory Potential Research Articles

A phase 1 trial of the MEK inhibitor selumetinib in combination with pembrolizumab for advanced or metastatic solid tumors

SummaryMEK inhibitors have immunomodulatory activity and potential for synergistic activity when combined with PD-1 inhibitors. We evaluated selumetinib (inhibitor of MEK1/2) plus pembrolizumab (anti‒PD-1 antibody) in patients with advanced/metastatic solid tumors. In this phase 1b study, adults with previously treated advanced/metastatic solid tumors received pembrolizumab 200 mg intravenously every 3 weeks plus selumetinib on days 1‒14 per 3-week cycle (2 weeks on/1 week off); selumetinib dosing began at 50 mg orally twice daily with escalation in 25 mg increments for ≤ 35 cycles. Primary endpoints were dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. Thirty-two patients were enrolled. Dose escalation was completed up to selumetinib 125 mg twice daily. The target DLT rate of 30% was not reached at any dose level. In the selumetinib 100 mg group, 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis). Dose-related changes in pharmacokinetic exposures were observed for selumetinib and N-desmethyl selumetinib up to 100 mg (saturation at 125 mg). Two patients achieved partial responses (1 each with selumetinib 75 mg and 125 mg) for an objective response rate of 6%. The study was stopped early because of insufficient efficacy. Although the target DLT rate was not reached at any dose level and no new safety signals were identified, selumetinib plus pembrolizumab had limited antitumor activity in this population. Trial registration: ClinicalTrials.gov, NCT03833427.

The Immunomodulatory Potential of Short-Chain Fatty Acids in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative central nervous system (CNS) disorder, characterized by focal inflammation, demyelination, irreversible axonal loss and neurodegeneration. The proposed mechanism involves auto-reactive T lymphocytes crossing the blood-brain barrier (BBB), contributing to inflammation and demyelination. Pro-inflammatory Th1 and Th17 lymphocytes are pivotal in MS pathogenesis, highlighting an imbalanced interaction with regulatory T cells. Dysbiosis in the gut microbiota, characterized by microbial imbalance is implicated in systemic inflammation, yet its exact role in MS remains elusive. Short-chain fatty acids (SCFAs), including valerate, butyrate, propionate, and acetate, produced through dietary fiber fermentation by the gut microbiota, modulate inflammation and immune responses. Particularly, butyrate and propionate exhibit pronounced anti-inflammatory effects in both the gut and CNS. These SCFAs influence regulatory T lymphocyte expression and BBB permeability. This review discusses the potential therapeutic implications of SCFA in MS, highlighting their ability to modulate the gut-brain axis and restore immune balance.

Immunomodulatory Effects of Vitamin D and Zinc on Viral Infection.

Several nutrients are crucial in enhancing the immune system and preserving the structural integrity of bodily tissue barriers. Vitamin D (VD) and zinc (Zn) have received considerable interest due to their immunomodulatory properties and ability to enhance the body's immune defenses. Due to their antiviral, anti-inflammatory, antioxidative, and immunomodulatory properties, the two nutritional powerhouses VD and Zn are crucial for innate and adaptive immunity. As observed with COVID-19, deficiencies in these micronutrients impair immune responses, increasing susceptibility to viral infections and severe disease. Ensuring an adequate intake of VD and Zn emerges as a promising strategy for fortifying the immune system. Ongoing clinical trials are actively investigating their potential therapeutic advantages. Beyond the immediate context of the pandemic, these micronutrients offer valuable tools for enhancing immunity and overall well-being, especially in the face of future viral threats. This analysis emphasizes the enduring significance of VD and Zn as both treatment and preventive measures against potential viral challenges beyond the current health crisis. The overview delves into the immunomodulatory potential of VD and Zn in combating viral infections, with particular attention to their effects on animals. It provides a comprehensive summary of current research findings regarding their individual and synergistic impacts on immune function, underlining their potential in treating and preventing viral infections. Overall, this overview underscores the need for further research to understand how VD and Zn can modulate the immune response in combatting viral diseases in animals.

Immunomodulatory and anticytokine therapeutic potential of three Indian spices constituents and its hyaluronic acid conjugates for prevention and post COVID-19 complications: a computational modeling approach.

Targeted drug delivery to SARS-CoV-2 host target proteins for preventing or blocking COVID-19 infection is making serious concern during COVID-19 pandemic and its consequent waves around the globe. People seek reliable, effective folkloric preventive medication for immediate and precautionary relief from COVID-19. These folkloric medicines were effective and saved many patients during the past COVID-19 pandemic. The current research study aims to deliver antiviral Indian spices phytocompounds and their hyaluronic acid conjugates to human host target proteins (ACE-2, TNF-α, IL-6, IL-1β, PAR-1) of SARS-CoV-2 to inhibit virus propagation and also to regulate early clinical complications of COVID-19. Targeted drug delivery of hyaluronic acid conjugated traditional natural bioactive agent produces more effective and fewer side effects in delivering novel drugs to human host proteins of COVID-19. In silico molecular docking study of six phytocompounds from three Indian spices and standard drug atazanavir and its hyaluronic acid conjugates reveals that phytocompounds and its hyaluronic acid conjugates possess high affinity to binding pockets of SARS-CoV-2 human host targets with more binding affinity scores. Most notably HA cyclocurcumin exhibit a docking score -9.9 kcal/mol against ACE-2 (PDB ID 1R42) target protein similarly HA-Hydrazinocurcumin exhibit a docking score -9.8 kcal/mol against PAR-1 (PDB ID 3VW7). ADMET validation of phytocompounds and their hyaluronic acid conjugates reveals its best pharmacokinetic profile over standard antiviral drug especially HA cyclocurcumin conjugate possesses high HIA (86%) and good pharmacokinetic profiles. DFT analysis affirms the reason behind the higher binding affinity of hyaluronic acid conjugates of spices phytocompounds towards all screened target proteins especially HA-hydrazinocurcumin conjugate possess high softness (19.1570 eV) and low hardness (0.0522 eV) values. Finally, MD simulation of best-docked compounds against ACE-2 and PAR-1 target protein revealed that hyaluronic acid conjugates of Indian spices compounds exhibit stable RMSD values and more protein-ligand interactions during simulation than hyaluronic acid conjugates of drug atazanavir.Communicated by Ramaswamy H. Sarma.

Comparative bioactivity and immunomodulatory potential of the new Bioroot Flow and AH Plus Bioceramic sealer: An in vitro study on hPDLSCs

ObjectivesTo evaluate the cytocompatibility, bioactivity, and anti-inflammatory potential of the new pre-mixed calcium silicate cement-based sealers Bioroot Flow (BrF) and AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared to the epoxy resin-based sealer AH Plus (AHP).Materials and methodsStandardized discs and 1:1, 1:2, and 1:4 eluates of BrF, AHPbcs and AHP after setting were prepared. The following assays were performed: cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, cytoskeleton organization via immunofluorescence staining; cytokine release via ELISA; osteo/cemento/odontogenic marker expression via RT-qPCR, and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars from healthy patients. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p < 0.05.ResultsBoth BrF and AHPbcs showed significantly positive results in the cytocompatibility assays (cell metabolic activity, migration, attachment, morphology, and cytoskeleton organization) compared with a negative control group, while AHP showed significant negative results. BrF exhibited an upregulation of at least one osteo/cementogenic marker compared to the negative and positive control groups. BrF showed a significantly higher calcified nodule formation than AHPbcs, the negative and positive control groups, while AHPbcs was higher than the negative control group. Both were also significantly higher than AHP group.ConclusionBrF and AHPbcs exhibit adequate and comparable cytocompatibility on hPDLSCs. BrF also promoted the osteo/cementogenic differentiation of hPDLSCs. Both calcium silicate-based sealers favored the downregulation of the inflammatory cytokine IL-6 and the calcified nodule formation from hPDLSCs. BrF exerted a significantly higher influence on cell mineralization than AHPbcs.Clinical relevanceThis is the first study to elucidate the biological properties and immunomodulatory potential of Bioroot Flow and AH Plus Bioceramic Sealer. The results act as supporting evidence for their use in root canal treatment.

Exploiting Leishmania-Primed Dendritic Cells as Potential Immunomodulators of Canine Immune Response.

Dendritic cells (DCs) capture pathogens and process antigens, playing a crucial role in activating naïve T cells, bridging the gap between innate and acquired immunity. However, little is known about DC activation when facing Leishmania parasites. Thus, this study investigates in vitro activity of canine peripheral blood-derived DCs (moDCs) exposed to L. infantum and L. amazonensis parasites and their extracellular vesicles (EVs). L. infantum increased toll-like receptor 4 gene expression in synergy with nuclear factor κB activation and the generation of pro-inflammatory cytokines. This parasite also induced the expression of class II molecules of major histocompatibility complex (MHC) and upregulated co-stimulatory molecule CD86, which, together with the release of chemokine CXCL16, can attract and help in T lymphocyte activation. In contrast, L. amazonensis induced moDCs to generate a mix of pro- and anti-inflammatory cytokines, indicating that this parasite can establish a different immune relationship with DCs. EVs promoted moDCs to express class I MHC associated with the upregulation of co-stimulatory molecules and the release of CXCL16, suggesting that EVs can modulate moDCs to attract cytotoxic CD8+ T cells. Thus, these parasites and their EVs can shape DC activation. A detailed understanding of DC activation may open new avenues for the development of advanced leishmaniasis control strategies.

Association between helminth infection and allergic disorders among children in Batu, Ethiopia.

Helminths are potent immunomodulators and in their chronic infection state they may protect against allergy-related disease and atopy. However, they are also known for inducing allergic conditions. This study aimed to assess the association between helminths, atopy and allergic conditions. A total of 461 school children participated in this cross-sectional study. Data on allergic symptoms and a range of confounding variables was gathered from parents via an interviewer-led questionnaire. Skin sensitization to house dust mite and cockroaches was analyzed, and a stool sample was collected for helminth analysis. Serum total Immunoglobulin E using enzyme-linked immunosorbent assay and eosinophil count were also measured. Overall sensitivity to both allergens was 2.4%. Self-reported allergic outcomes in the last 12 months for the 461 participants had been : wheezing 3.7%, asthma 2.2%, eczema 13.2% and hay fever 6.9%. Overall, the prevalence of helminth infection was 11.9% (53/444). A borderline significant association was found between atopy and any allergy symptoms (odds ratio [OR]: 3.32, 95% confidence interval [95% CI: 0.99, 11.1], p = .052). There was no significant association between helminths and atopy (OR: 0.64 [95% CI: 0.29, 1.41], p = .268) and also between helminths and allergic symptoms (OR: 0.64 [95% CI: 0.29, 1.41], p = .268). Bivariate analysis showed keeping an animal in the house increases the risk of atopy while maternal and paternal history of allergy increases the risk of developing allergic symptoms in the children. This study found a non-significant inverse association between helminths infection and atopy and allergic disorders, likely due to reduced statistical power, resulting in a lower prevalence of atopy and allergic conditions. A high powered longtitudinal study is necessary to explore the casuality and potential therapeutic benefits of helminths for allergic disorders.

Mechanistic Roles of Different Varieties of Honey on Wound Healing: Recent Update

Background Honey has been used for centuries for its medicinal benefits, where topical treatments in the folklore literature reported its beneficial role in treating different types of wounds. Despite its immense use in wound care, honey’s exact mechanism remains unclear. Purpose The present study aimed to explore and abridge the gap between honey and its molecular wound healing mechanism. Methodology An extensive literature study has been performed where these activities can be explained due to phenolic compounds, nitric oxide, non-peroxide factors, low pH, high osmolarity, and hydrogen peroxide in honey. Besides that, honey also contains carbohydrates, proteins, amino acids, lipids, minerals, and vitamins, contributing to the wound healing potential to some extent. However, these metabolites and constituents differ among different honey varieties due to the distinct nutritional requirements of different species of bees and their collection of nectar from varied sources containing different natural actives. Results The revival of honey-based wound care research has identified a few probable mechanistic pathways of honey primarily due to its anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory potentials. It also promotes angiogenesis, facilitates reepithelialization, stimulates proliferation of extracellular matrix, reduces neutrophil formation, modulates production of TNF-α, IL-1β, and IL-6, and prevents secondary infection at the wound site. Conclusion The varieties of honey vary in their qualities, phenolic compounds, and safety for human use. A few of these are currently clinically employed for wound dressings. Moreover, honey can be effective for managing complicated and chronic wounds; more extensive molecular research and safety profiling would be necessary.

MSC-Derived Exosomes Mitigate Myocardial Ischemia/Reperfusion Injury by Reducing Neutrophil Infiltration and the Formation of Neutrophil Extracellular Traps.

Acute inflammatory storm is a major cause of myocardial ischemia/reperfusion (I/R) injury, with no effective treatment currently available. The excessive aggregation of neutrophils is correlated with an unfavorable prognosis in acute myocardial infarction (AMI) patients. Exosomes derived from mesenchymal stromal cells (MSC-Exo) have certain immunomodulatory potential and might be a therapeutic application. Therefore, we investigated the protective role of MSC-Exo in modulating neutrophil infiltration and formation of neutrophil extracellular traps (NETs) following myocardial I/R injury. Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. We used flow cytometry, histochemistry, and immunofluorescence to detect the changes of neutrophils post-intravenous MSC-Exo injection. Additionally, cardiac magnetic resonance (CMR) and thioflavin S experiments were applied to detect microvascular obstruction (MVO). The NLR family pyrin domain containing 3 (NLRP3) inflammasome was examined for mechanism exploration. Primary neutrophils were extracted for in vitro experiment. Antibody of Ly6G was given to depleting the neutrophils in mice for verification the effect of MSC-Exo. Finally, we analyzed the MiRNA sequence of MSC-Exo and verified it in vitro. MSC-Exo administration reduced neutrophil infiltration and NETs formation after myocardial I/R. MSC-Exo treatment also could attenuate the activation of NLRP3 inflammasome both in vivo and in vitro. At the same time, the infarction size and MVO following I/R injury were reduced by MSC-Exo. Moreover, systemic depletion of neutrophils partly negated the therapeutic effects of MSC-Exo. Up-regulation of miR-199 in neutrophils has been shown to decrease the expression of NETs formation after stimulation. Our results demonstrated that MSC-Exo mitigated myocardial I/R injury in mice by modulating neutrophil infiltration and NETs formation. This study provides novel insights into the potential therapeutic application of MSC-Exo for myocardial ischemia/reperfusion injury.

HLA-DRB1*15:01 and the MERTK Gene Interact to Selectively Influence the Profile of MERTK-Expressing Monocytes in Both Health and MS.

HLA-DRB1*15:01 (DR15) and MERTK are 2 risk genes for multiple sclerosis (MS). The variant rs7422195 is an expression quantitative trait locus for MERTK in CD14+ monocytes; cells with phagocytic and immunomodulatory potential. We aimed to understand how drivers of disease risk and pathogenesis vary with HLA and MERTK genotype and disease activity. We investigated how proportions of monocytes vary with HLA and MERTK genotype and disease activity in MS. CD14+ monocytes were isolated from patients with MS at relapse (n = 40) and 3 months later (n = 23). Healthy controls (HCs) underwent 2 blood collections 3 months apart. Immunophenotypic profiling of monocytes was performed by flow cytometry. Methylation of 35 CpG sites within and near the MERTK gene was assessed in whole blood samples of individuals experiencing their first episode of clinical CNS demyelination (n = 204) and matched HCs (n = 345) using an Illumina EPIC array. DR15-positive patients had lower proportions of CD14+ MERTK+ monocytes than DR15-negative patients, independent of genotype at the MERTK SNP rs7422195. Proportions of CD14+ MERTK+ monocytes were further reduced during relapse in DR15-positive but not DR15-negative patients. Patients homozygous for the major G allele at rs7422195 exhibited higher proportions of CD14+ MERTK+ monocytes at both relapse and remission compared with controls. We observed that increased methylation of the MERTK gene was significantly associated with the presence of DR15. DR15 and MERTK genotype independently influence proportions of CD14+ MERTK+ monocytes in MS. We confirmed previous observations that the MERTK risk SNP rs7422195 is associated with altered MERTK expression in monocytes. We identified that expression of MERTK is stratified by disease in people homozygous for the major G allele of rs7422195. The finding that the proportion of CD14+ MERTK+ monocytes is reduced in DR15-positive individuals supports prior data identifying genetic links between these 2 loci in influencing MS risk. DR15 genotype-dependent alterations in methylation of the MERTK gene provides a molecular link between these loci and identifies a potential mechanism by which MERTK expression is influenced by DR15. This links DR15 haplotype to MS susceptibility beyond direct influence on antigen presentation and suggests the need for HLA-based stratification of approaches to MERTK as a therapeutic target.

Mechanoregulation of MSC spheroid immunomodulation.

Mesenchymal stromal cells (MSCs) are widely used in cell-based therapies and tissue regeneration for their potent secretome, which promotes host cell recruitment and modulates inflammation. Compared to monodisperse cells, MSC spheroids exhibit improved viability and increased secretion of immunomodulatory cytokines. While mechanical stimulation of monodisperse cells can increase cytokine production, the influence of mechanical loading on MSC spheroids is unknown. Here, we evaluated the effect of controlled, uniaxial cyclic compression on the secretion of immunomodulatory cytokines by human MSC spheroids and tested the influence of load-induced gene expression on MSC mechanoresponsiveness. We exposed MSC spheroids, entrapped in alginate hydrogels, to three cyclic compressive regimes with varying stress (L) magnitudes (i.e., 5 and 10 kPa) and hold (H) durations (i.e., 30 and 250 s) L5H30, L10H30, and L10H250. We observed changes in cytokine and chemokine expression dependent on the loading regime, where higher stress regimes tended to result in more exaggerated changes. However, only MSC spheroids exposed to L10H30 induced human THP-1 macrophage polarization toward an M2 phenotype compared to static conditions. Static and L10H30 loading facilitated a strong, interlinked F-actin arrangement, while L5H30 and L10H250 disrupted the structure of actin filaments. This was further examined when the actin cytoskeleton was disrupted via Y-27632. We observed downregulation of YAP-related genes, and the levels of secreted inflammatory cytokines were globally decreased. These findings emphasize the essential role of mechanosignaling in mediating the immunomodulatory potential of MSC spheroids.

The effect of UVA light/8-methoxypsoralen exposure used in Extracorporeal Photopheresis treatment on platelets and extracellular vesicles.

Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to Ultra Violet A light (UVA)/8-methoxypsoralen is currently unknown. Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalen in vitro and platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatment in vitro does not induce platelet aggregation or significantly alter levels of the platelet activation markers, soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECP in vitro does not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistent in vivo.

The future of cow's milk allergy - milk ladders in IgE-mediated food allergy.

Cow's milk allergy (CMA) is one of the most common and complex presentations of allergy in early childhood. CMA can present as IgE and non-IgE mediated forms of food allergy. Non-IgE mediated CMA includes food protein-induced enterocolitis syndrome (FPIES), eosinophilic gastrointestinal disorders (EGIDs), and food protein-induced proctocolitis (FPIAP). There are recent guidelines addressing CMA diagnosis, management, and treatment. Each of these guidelines have their own strengths and limitations. To best manage CMA, individualized avoidance advice should be given. Cow's milk (CM) can be replaced in the diet by using hypoallergenic formulas or plant-based milk, depending on factors such as the child's age and their current food intake. Oral and epicutaneous immunotherapy is used to increase tolerance in children with CMA but is not without risk, and the long-term outcome of sustained unresponsiveness is still unclear. The allergenicity of CM proteins are affected differently by different forms of heating, leading to the use of baked milk or milk ladders in the management of CMA, most likely the most promising option for future management and treatment of CMA. Future management of children with CMA will also include discussion around the immunomodulatory potential of the child's dietary intake.

Chemoprotective and immunomodulatory potential of Lactobacillus reuteri against cadmium chloride-induced breast cancer in mice

IntroductionThe current study aimed to investigate the role of probiotic Lactobacillus reuteri for the treatment and prevention of breast cancer. Materials and methodsBreast cancer was induced by using Cadmium Chloride (Cd) (2 mg/kg) in group II. Tamoxifen was administered to group III. Group IV was treated with Lactobacillus reuteri. Group V was treated with Cd for one month and divided into three subgroups including VA, VB, and VC which were treated with tamoxifen, Lactobacillus reuteri, and tamoxifen + Lactobacillus reuteri, respectively. ResultsSignificantly higher levels of TNF-α (40.9 ± 4.2 pg/mL), IL-6 (28.0 ± 1.5 pg/mL), IL-10 (60.2 ± 2.0 pg/mL), IFN-γ (60.2 ± 2.0 pg/mL), ALAT (167.2 ± 6.2 U/l), ASAT (451.6 ± 13.9 U/l), and MDA (553.8 ± 19.6 U/l) was observed in Cd group. In comparison, significantly lower levels of TNF-α (18.0 ± 1.1 pg/mL), IL-6 (9.4 ± 0.4 pg/mL), IL-10 (20.8 ± 1.1 pg/mL), IFN-γ (20.8 ± 1.1 pg/mL), ALAT (85.2 ± 3.6 U/l), ASAT (185 ± 6.9 U/l), and MDA (246.0 ± 7.5 U/l) were observed in group Cd + Tam + LR. Liver histopathology of the Cd group showed hemorrhage and ductal aberrations. However, mild inflammation and healthier branched ducts were observed in treatment groups. Furthermore, the renal control group showed normal glomerular tufts, chronic inflammation from the Cd group, and relatively healthier glomerulus with mild inflammation in treatment groups. ConclusionHence, the preventive and anticancerous role of probiotic Lactobacillus reuteri is endorsed by the findings of the current study.

Cytochalasins as Modulators of Stem Cell Differentiation.

Regenerative medicine aims to identify new research strategies for the repair and restoration of tissues damaged by pathological or accidental events. Mesenchymal stem cells (MSCs) play a key role in regenerative medicine approaches due to their specific properties, such as the high rate of proliferation, the ability to differentiate into several cell lineages, the immunomodulatory potential, and their easy isolation with minimal ethical issues. One of the main goals of regenerative medicine is to modulate, both in vitro and in vivo, the differentiation potential of MSCs to improve their use in the repair of damaged tissues. Over the years, much evidence has been collected about the ability of cytochalasins, a large family of 60 metabolites isolated mainly from fungi, to modulate multiple properties of stem cells (SCs), such as proliferation, migration, and differentiation, by altering the organization of the cyto- and the nucleo-skeleton. In this review, we discussed the ability of two different cytochalasins, cytochalasins D and B, to influence specific SC differentiation programs modulated by several agents (chemical or physical) or intra- and extra-cellular factors, with particular attention to human MSCs (hMSCs).

Immuno-Enhancing Effects of Galium aparine L. in Cyclophosphamide-Induced Immunosuppressed Animal Models.

This study investigates the immunomodulatory potential of Galium aparine L. (GAE) in immunodeficient animals. In this study, animals were categorized into five groups: the normal group, CYP group (cyclophosphamide intraperitoneal injection), GA5 group (cyclophosphamide + 5 μg GAE), GA50 group (cyclophosphamide + 50 μg GAE), and GA500 group (cyclophosphamide + 500 μg GAE). The CYP group exhibited significantly reduced spleen weights compared to the normal group, while the groups obtaining GAE displayed a dose-dependent increase in spleen weight. Furthermore, the GAE demonstrated dose-dependent enhancement of splenocyte proliferating activity, with significant increases observed in both LPS and ConA-induced assays. NK cell activity significantly increased in the GA50 and GA500 groups compared to the CYP group. Cytokine analysis revealed a significant increase in IL-6, TNF-α, and IFN-γ levels in ConA-induced splenocytes treated with GAE. Gene expression analysis identified 2434 DEG genes in the extract groups. Notable genes, such as Entpd1, Pgf, Thdb, Syt7, Sqor, and Rsc1al, displayed substantial differences in individual gene expression levels, suggesting their potential as target genes for immune enhancement. In conclusion, Galium aparine L. extract exhibits immunomodulatory properties. The observed gene expression changes further support the potential of Galium aparine L. extract as a natural agent for immune augmentation.

Immunomodulating Potential of Ekebergia capensis in Murine Schistosoma mansoni Juvenile and Adult Infection

Schistosomiasis is a neglected tropical disease occurring in sub-Saharan Africa and affecting almost 250 million people. The drug of choice for treatment for Schistosomiasis has been Praziquantel which has been used for many years and there is a need to develop new drugs. The immunomodulatory potential of Ekebergia capensis extract on both juvenile and adult Schistosoma mansoni infection in vivo was evaluated in this study. Swiss albino mice were infected individually with 90 S. mansoni cercariae and randomized into groups of five each for i) plant extract treated groups ii) positive control groups treated with conventional drugs PZQ or artemether iii) infected but untreated (negative control) groups. The mice were treated orally with aqueous extracts of E. capensis at doses of 200 and 400 mg/kg at 2 weeks (juvenile worms) and 7 weeks (adult worms) post-infection. Immune immune-enhancing potential of the medicinal plant was determined by analyzing the levels of cytokines in serum samples that were collected before and after treatment. A BD-Cytometric Bead Array (CBA) mouse Th1/Th2/Th17 kit was used to quantitate the levels of cytokines using a flow cytometer (FACS Calibur) and analysis of the data was done using FCAP software. Results indicated that the medicinal plant extract had an immunomodulatory effect. There was a significant increase (P&lt;0.05) in Th1 cytokines (IL-2, IFN- γ and TNF-α), a decrease in Th2 cytokines (IL-4, IL-6 and IL-10) and an increase in Th17 (IL-17). These findings confirm the potential use of medicinal plants in the management of schistosomiasis.

Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies.

Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.

Wine is more than just a beverage: Chemical diversity, health benefits, and immunomodulating potential of wine polyphenols

AbstractWine, the fermented juice of the grape (Vitis vinifera), is a complex beverage composed primarily of water and ethanol. On the other hand, phenolic compounds are less abundant components that participate in taste and color formation. In addition to their major role in the sensory profile of wine, phenolic compounds (also referred as polyphenols) function through various mechanisms, exerting positive influence on health. According to recent research, consuming just one glass of red wine positively contributes to health protection, and it is connected to the maintenance of the redox endothelial balance, potential for reducing diabetes occurrence, preventing atherosclerosis, and reducing the risk of cardiovascular diseases. What is more, a lower incidence of certain types of cancers has also been observed. The health promoting benefits of wine are explained by its wide spectrum of structurally diverse phenolic compounds whose content may depend on numerous factors. The most abundant compounds are anthocyanins with up to 400 mg/L, followed by phenolic acids, flavanols, flavonols, hydrolyzable tannins, flavanones, and stilbenes (up to 200, 120, 60, 50, 25, and 5 mg/L, respectively). This review paper outlines the structural variety, health advantages, and immunomodulatory capacity of wine polyphenols, drawing upon the latest and most pertinent scientific literature available in this domain.

Impact of cold atmospheric pressure plasma (CAPP) treatments on the prebiotic potential of Arthrospira platensis (Spirulina)

Powdered Arthrospira platensis (Spirulina) is one of the most valuable nutraceutical products in terms of functionality and food-fortification due to its recognized prebiotic, antioxidant, and immunomodulatory potential. The present study aims to assess the quality of this matrix as a prebiotic after Cold Atmospheric Pressure Plasma (CAPP) processing. CAPP-treated Spirulina samples (1 mg/mL), at effective discharge power of 1.1, 1.7, 2.2 and 3.3 W for 5 min, were used to promote the growth of the probiotics Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus GG. Chicory inulin was used as reference prebiotic material (1 mg/mL). - Microorganisms were inoculated in the different prepared media, and incubated 48 h, at 30 °C, under anaerobic conditions. The probiotics' growth rate on Spirulina (CAPP treated and untreated) dispersions, protein stability and their secondary metabolites production were evaluated. The bacterial growth (>7.0 ± 0.2 log10 cycles) and prebiotic indices of treated Spirulina samples (compared to untreated Spirulina) confirm the prebiotic functionality before and after CAPP processing. The proteomic and metabolomic profiles of the hydrolyzed matrix post-fermentation revealed significant differences in the nutritional values of the final fermented product, depending on the applied CAPP intensity. The present study provides first-time insight into CAPP optimization for increased bioavailability of Spirulina compounds and quality proofed nutraceutical development.