Immunomodulatory Effects Research Articles

Research progress of natural products targeting tumor-associated macrophages in antitumor immunity: A review.

As an important innate immune cell in the body, macrophages have a strong ability to phagocytic tumor cells and maintain the innate immune response. Tumor-associated macrophages play a more prominent role in regulating tumor immunity and are currently an important target of antitumor immunity. As a new type of antitumor therapy, tumor immunotherapy has great potential, combined chemotherapy, targeting and other therapeutic means can significantly enhance the antitumor therapy effect. At present, a number of natural products have been proved to have significant immunomodulatory and antitumor effects, and have become a hot field of antitumor immunity research. Studies have found that a variety of natural products, such as polysaccharides, flavonoids, saponins, lactones, and alkaloids, can induce the polarization of M1 macrophages, inhibit the polarization of M2 macrophages, and regulate the expression of immune-related cytokines by targeting specific signaling pathways to enhance the killing effect of macrophages on tumor cells and improve the tumor immune microenvironment, and finally better play the antitumor immune function. In this paper, by summarizing the research results of the specific mechanism of natural products targeting tumor-associated macrophages to exert antitumor immunity in recent years, we discussed the aspects of natural products targeting tumor-associated macrophages to enhance antitumor immunity, in order to provide a new research idea for tumor immunotherapy and further improve the effectiveness of clinical antitumor therapy.

Phytochemicals from Passiflora coriacea Juss. Have Anti-Inflammatory and Neuroprotective Effects in Mouse Models.

Background: Neuroinflammatory diseases trigger an inflammatory response and a state of oxidative stress. Passiflora coriacea Juss. has been used to treat conditions related to inflammatory processes in the central nervous system; however, to date, there has been no study on the anti-inflammatory and neuroprotective effects of this species. Methods: The anti-inflammatory effect of P. coriacea was evaluated in a TPA-induced auricular edema model, and the percentage of edema inhibition (Ei) was recorded. The Morris water maze was used to assess the neuroprotective effect, measuring the latency time (LT), and lipopolysaccharide was administered to induce neuroinflammation. The concentrations of cytokines (IL-6, IL-10, and TNF-α) and activities of antioxidant system components (CAT, SOD, GR, NO, and MDA) were measured in the mouse brains. The chemical composition was determined using chromatographic and nuclear magnetic resonance techniques. Results: T1.1, T2.1, and T3.1 showed anti-inflammatory (Ei = 92.5, 88.3, and 64.8%, respectively) and neuroprotective (LT = 27.2, 22.9, and 27.7 s, respectively) effects. T1.1 was identified as scopolin with immunomodulatory (IL-6 = 3307 pg/g) and antioxidant (CAT = 1198 mmol, SOD = 23%, GR = 5.34 units/mL, NO = 11.5 µM, MDA = 1526 nmol/mL) effects; T2.1 was a mixture of terpenes (fitone, 7-dehydrodiosgenin, tremulone) with immunomodulatory (TNF-α = 857 pg/g) and antioxidant (CAT = 1245 mmol, NO = 8.75 µM) effects; and T3.1 was a mixture of isoquercetin and astragalin with immunomodulatory (IL-6 = 3135 pg/g, IL-10 = 1300 pg/g, TNF-α = 751 pg/g) and antioxidant (SOD = 1204 nmol/mL, CAT = 1131 nmol/mL, NO = 6.37 µM, MDA = 1204 nmol/mL) effects. Conclusions: The administration of P. coriacea treatments generated anti-inflammatory, neuroprotective, immunomodulatory, and antioxidant effects. These effects are attributable to its chemical composition, comprising scopolin, terpenes, and a mixture of isoquercetin and astragalin, which have not previously been described in this species.

Exopolysaccharides from Bifidobacterium longum subsp. infantis and Bifidobacterium adolescentis modulate Toll-like receptor signaling

BackgroundExopolysaccharides (EPS) from probiotic bacteria like bifidobacteria, have gained considerable attention for the beneficial effects they exert in the gastrointestinal environment. Here, we investigated whether EPS isolated from Bifidobacterium longum subsp. infantis and Bifidobacterium adolescentis can interact with Toll-like receptors (TLRs) in a structure-dependent way and subsequently we investigated whether they influence cytokine-production in dendritic cells (DCs). ResultsEPS from both B. infantis and B. adolescentis were found to be structurally different and were able to inhibit signaling of TLR2 and TLR4 in an EPS-type dependent fashion. EPS from B. infantis was shown to have stronger inhibitory effects on TLR2/1, whereas EPS from B. adolescentis showed stronger effects for TLR2/6 and TLR4. Incubation of DCs with EPS alone had no effect, however stimulation of DCs with spend-medium of epithelial cells incubated with EPS reduced production of the cytokines MCP-1/CCL2 and TNFα. ConclusionHere we show that EPS from B. infantis and B. adolescentis have structure-dependent immunomodulatory effects, indicating that EPS might be important effector molecules responsible for the health benefits of bifidobacteria.

The potential of lactoferrin as antiviral and immune-modulating agent in viral infectious diseases.

Emerging infectious diseases are caused by unpredictable viruses with the dangerous potential to trigger global pandemics. These viruses typically initiate infection by utilizing the anionic structures of host cell surface receptors to gain entry. Lactoferrin (Lf) is a multifunctional glycoprotein with multiple properties such as antiviral, anti-inflammatory and antioxidant activities. Due to its cationic structure, Lf naturally interacts with certain host cell receptors, such as heparan sulfate proteoglycans, as well as viral particles and other receptors that are targeted by viruses. Therefore, Lf may interfere with virus-host cell interactions by acting as a receptor competitor for viruses. Herein we summarize studies in which this competition was investigated with SARS-CoV-2, Zika, Dengue, Hepatitis and Influenza viruses in vitro. These studies have demonstrated not only Lf's competitive properties, but also its potential intracellular impact on host cells, such as enhancing cell survival and reducing infection efficiency by inhibiting certain viral enzymes. In addition, the immunomodulatory effect of Lf is highlighted, as it can influence the activity of specific immune cells and regulate cytokine release, thereby enhancing the host's response to viral infections. Collectively, these properties promote the potential of Lf as a promising candidate for research in viral infectious diseases.

Infection Risk Associated with High-Efficacy Disease-Modifying Agents in Multiple Sclerosis: A Retrospective Cohort Study.

In patients with multiple sclerosis (MS), infections represent a significant concern, particularly given the immunomodulatory effects of disease-modifying agents (DMAs). High-efficacy DMAs (heDMAs) play a pivotal role in delaying MS progression, yet their use also raises concerns regarding the risk of infection. This study aimed to compare the infection risk with the use of heDMA and moderate-efficacy disease-modifying agents (meDMAs) in MS patients. This retrospective cohort study involved adult (18-64 years) MS patients with incident DMA use based on the 2015-2019 MarketScan Commercial Claims and Encounters Database. Patients initiating heDMAs (natalizumab, alemtuzumab, and ocrelizumab) or meDMAs (interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and glatiramer acetate) were included. The outcomes of interest were comparative risk of overall infection, serious infection, and frequently reported types of infection. Adjusted hazard ratios (aHR) were estimated in inverse probability treatment weighting (IPTW) based on Cox proportional hazard models. Among 10,003 eligible incident DMA users, 22.92% of patients initiated heDMAs. The IPTW-CPH model revealed that patients with heDMAs were associated with a higher risk of serious infection (aHR: 1.24, 95% confidence interval (CI): 1.06-1.44) and urinary tract infection (UTI; aHR: 1.21, 95% CI: 1.14-1.30). Sensitivity analyses with different follow-up periods yielded consistent findings with the main analyses. In MS, heDMAs were associated with a greater risk of serious infection and UTI compared with meDMAs. These findings suggest the need to carefully monitor and manage the infection risk to optimize the use of heDMAs in MS.

Cervical cancer as an example: Exploring the value of exosomes in cancer diagnosis and treatment

Abstract. Based on the characteristics that exosomes are generated by virtually all cellular phenotypes as well can carry non-coding RNA as an intercellular communication medium, as well as the important contribution of exosomes derived from tumors to the processes of tumorigenesis and tumor progression, this paper analyzed the part of exosomes in cancer therapy by taking cervical cancer as an example, and briefly analyzed their functions in the treatment of lung cancer and gastric cancer. At present, exosomes have gradually become an important research object for tumor regulation and treatment due to their rich contents and diverse functions. This paper studies the clinical character of exosomes in disease treatment from the three types of non-coding RNAs carried by exosomes and the immunomodulative effects of exosomes themselves. In view of the fact that the application of exosomes in cancer treatment has been partially popularized, there is still a lack of advantages and theoretical research on exosomes in the treatment of cancer. In this paper, the therapeutic effect of exosomes on cervical cancer is mainly studied and analyzed by using the characteristics of exosome mi RNA, which is highly specific and can inhibit tumor cells.

Immunomodulatory effects of HYCO-3, a dual action CO-releaser/Nrf2 activator.

HYCOs are hybrid molecules consisting of activators of the transcription factor Nrf2 conjugated to carbon monoxide (CO)-releasing moieties. These "dual action" compounds have been designed to mimic the activity of heme oxygenase-1 (HO-1), a stress inducible cytoprotective enzyme that degrades heme to CO which expression is regulated by Nrf2. HYCOs have recently shown efficacy in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, the mechanism(s) of action of HYCOs still remain to be fully investigated. Here, we assessed the effects of HYCO-3, a prototype of these hybrids, on myeloid-derived cells, microglial cells and T lymphocytes obtained from EAE-immunized mice. HYCO-3 exerted immunomodulatory effects on all the examined cell populations by inhibiting the generation of pro-inflammatory cytokines and nitric oxide, and downregulating antigen-presenting capacity of these cells. The observed effects support the view that HYCOs are promising candidates to be developed for the treatment of autoimmune and chronic inflammatory disorders.

Antibacterial bioadaptive scaffold promotes vascularized bone regeneration by synergistical action of intrinsic stimulation and immunomodulatory activity

The coupling of angiogenesis and osteogenesis is the fundamental necessity in bone fracture healing, thus simulative action of tissue-engineered bone provides powerful and beneficial effects in the treatment of bone defect. Herein, an immunoregulatory biocomposite scaffold with intrinsic activities of coupling angiogenesis and osteogenesis was constructed based on polyelectrolytes-modified 3D-printed scaffold for enhanced bone regeneration. The doping of Sr-doped hydroxyapatite (SrHA) within 3D-printed polycaprolactone (PCL) scaffold and subsequent slit guidance ligand 3 (SLIT3) protein adsorption through surface coating of carboxymethyl chitosan (CCS)/hyperbranched polylysine (HBPL) achieved on-demand delivery of SLIT3 and Sr ions. The antibacterial property of polyelectrolytes-modified scaffold was characterized and was directly proportional to the layer number of polyelectrolytes coating. The dual-factor delivery scaffold had good biocompatibility to support cell proliferation and migration, and was capable of stimulating angiogenesis and osteogenesis by intrinsic stimulation from released SLIT3 protein and Sr ions. Importantly, the multifunctional scaffold had immunomodulatory effects of promoting M2-type polarization of macrophages and thereby increasing anti-inflammatory factors level, as well as indirectly promoting angiogenesis and osteogenesis. The in vivo experiments revealed that the anti-inflammatory effect was significantly reinforced for providing a better regenerative microenvironment and bone regeneration capacity was dramatically enhanced accompanied with type H vessels formation when implanted with multifunctional scaffold. Therefore, the bioadaptive scaffold possessed amplified bone regeneration performance through intrinsic stimulation and immunomodulatory effects, suggesting a promising therapeutic candidate for bone defect repair.

Analysis of Microheterogeneous Glutelin Subunits and Highly Efficient Identification of Selenylation Peptides by In-Gel Proteolysis: Focus on Se-Enriched Rice.

Selenylation of cysteine and methionine thiols through selenate supplements increases the content of selenium-containing amino acids in various agricultural products. This modification results in numerous biological and health benefits. Despite their critical roles in human physiology, methods for high-coverage and efficient identification of selenylation peptides are limited. This study systematically developed a mass spectrometric method to identify selenylation peptides combined with in-gel trypsin proteolysis. In-gel proteolysis identified the two well-separated bands containing rice glutelin. We identified 11 rice glutelin subunits along with 42 selenylation peptides from the glutelin acidic subunits and 30 selenylation peptides from the glutelin basic subunits with high confidence. A comprehensive evaluation disclosed the mapping of selenium-containing rice glutelin subunits. Additionally, the selenylation modification of peptides coexisted with oxidation and iodoacetamide (IAM) alkylation. Moreover, the multidimensional MS criteria validated the results, while spectral statistics revealed the veritable Se/S substitution degree in Se-enriched rice. These findings collectively demonstrated the presence of numerous selenation sites in microheterogeneous glutelin subunits, thereby enhancing our understanding of the seleno-peptidomics of rice proteins. As significant bioactive organic compounds, the identified peptides in this study are promising candidates for a variety of bioactivities, including neuroprotective, anti-inflammatory, antioxidant, hepatoprotective, and immunomodulatory effects.

Mannose/stearyl chloride doubly functionalized polyethylenimine as a nucleic acid vaccine carrier to promote macrophage uptake

Transmembrane transport remains a significant challenge for nucleic acid vaccine vectors. Promoting the ability of immune cells, such as macrophages, to capture foreign stimuli is also an effective approach to improving cross-presentation. In addition, polyethyleneimine (PEI) has gained attention in the field of nucleic acid vaccine carriers due to its excellent gene transfection efficiency and unique proton buffering effect. However, although high molecular weight PEI exhibits high efficiency, its high-density positive charges make it highly toxic, which limits its application. In this study, mannose/stearyl chloride functionalized polyethylenimine (SA-Man-PEI) was prepared by functionalizing PEI (molecular weight of 25 kDa) with mannose with immunomodulatory and phagocyte targeting effects, and an alkyl hydrophobic chain segment, which could easily promote cell uptake. Moreover, the functionalized-PEI retains a strong proton buffering effect, which helps the carrier escape from the lysosome. The particle sizes of the composite particles formed by SA-Man-PEI and ovalbumin (OVA) were below 200 nm, with good storage stability at both 4 °C and 37 °C. At a drug concentration of 2 μg/mL, the cell survival rate of functionalized-PEI was 19.2% higher than that of unfunctionalized PEI. In vitro macrophage endocytosis experiments showed that SA-Man-PEI could significantly enhance the macrophage uptake of composite particles, compared to unfunctionalized PEI or single-functionalized PEI. This study offers a new approach for developing PEI as a nucleic acid vaccine carrier, which could simultaneously enhance cell targeting and promote cell uptake.

Lactobacillus johnsonii JERA01 upregulates the production of Th1 cytokines and modulates dendritic cells-mediated immune response.

Lactic acid bacteria are known to have various effects on the immune system. The type and extent of the effect differ, depending on the type of lactic acid bacteria. This study aimed to investigate the effects of Lactobacillus johnsonii bacterin on mouse-derived immune cells. Treating splenocytes with L. johnsonii bacterin slightly increased the metabolic activity. Additionally, the expression of the activation marker CD25 and production of the Th1-type inflammatory cytokine interferon (IFN)- gamma increased. We confirmed that the increase in IFN-gamma production due to L. johnsonii stimulation was mainly due to T and B cells among splenocytes. Treating dendritic cells (DCs) with L. johnsonii bacterin at concentrations of 106 and 107 cfu/ ml significantly increased tumor necrosis factor-alpha, a pro-inflammatory cytokine, and interleukin-12, a cell-mediated immunity cytokine. Additionally, the expression of surface markers increased. Allogeneic mixed lymphocyte reactions showed that L. johnsonii reduced the antigen-presenting ability of DCs. In cocultures of DCs and splenocytes, L. johnsonii decreased cellular metabolic activity and increased cell death. L. johnsonii upregulated the expression of programmed death ligand 1 on DCs. The findings of this study indicate that L. johnsonii bacterin has immunomodulatory and immunostimulatory effects. While L. johnsonii increased the expression of cytokines and surface markers of immune cells, it modulated DC-mediated immune response. Further studies are needed to determine the effects of L. johnsonii bacterin on DCs and related immune cells.

Immortalized mammosphere-derived epithelial cells retain a bioactive secretome with antimicrobial, regenerative, and immunomodulatory properties

BackgroundThe secretome of primary bovine mammosphere-derived epithelial cells (MDECs) has been shown to exert antimicrobial, regenerative, and immunomodulatory properties in vitro, which warrants its study as a potential biologic treatment with the potential to be translated to human medicine. Currently, the use of the MDEC secretome as a therapy is constrained by the limited life span of primary cell cultures and the decrease of secretome potency over cell passages.MethodsTo address these limitations, early-passage bovine MDECs were immortalized using hTERT, a human telomerase reverse transcriptase. The primary and immortal MDECs were compared morphologically, transcriptomically, and phenotypically. The functional properties and proteomic profiles of the secretome of both cell lines were evaluated and compared. All experiments were performed with both low and high passage cell cultures.ResultsWe confirmed through in vitro experiments that the secretome of immortalized MDECs, unlike that of primary cells, maintained antimicrobial and pro-migratory properties over passages, while pro-angiogenic effects of the secretome from both primary and immortalized MDECs were lost when the cells reached high passage. The secretome from primary and immortalized MDECs, at low and high passages exerted immunomodulatory effects on neutrophils in vitro.ConclusionsHigh passage immortalized MDECs retain a bioactive secretome with antimicrobial, regenerative, and immunomodulatory properties, suggesting they may serve as a consistent cell source for therapeutic use.

Harnessing Tumor Cell-Derived Exosomes for Immune Rejection Management in Corneal Transplantation.

Transplantation remains the definitive treatment for end-stage organ failures, but its efficacy is frequently compromised by immune rejection. This study introduces a novel strategy by utilizing tumor-derived exosomes from B16-F10 melanoma cells (B16-Exo), diverging from the conventional use of immune cell-derived exosomes, to alleviate post-transplantation immune rejection. Utilizing murine corneal transplantation as a model, it is demonstrated that B16-Exo significantly reduces immune rejection, evidenced by decreased corneal opacity, neovascularization, and immune dysregulation, while enhancing postoperative survival. Proteomic analyses reveal differential expression of pivotal proteins in B16-Exo, notably the JAK2 protein within the JAK-STAT signaling pathway, which has been mechanistically demonstrated to amplify the activity of myeloid-derived suppressor cells (MDSCs) and inhibit T cell proliferation. These findings demonstrate the significant immunomodulatory effect of B16-Exo in transplant immunology, supporting the continued exploration of tumor-derived exosomes as a platform to uncover novel immunosuppressive mechanisms in transplantation.

Influence of glycodelin on the formation of immune response at the level of T-helpers and T-regulatory cells in an <i>in vivo</i> experiment

Objective. To study the influence of glycodelin on T-helpers and Tregs level in the process of forming an immune response to the introduction of allogeneic bone marrow (BM) cells in a dynamic experiment on Wistar rats. Materials and methods. The original experimental model "host versus transplant reaction" on male Wistar rats without preliminary conditioning in recipients was used in the study. Animals were administered recombinant glycodelin against the background of allogeneic intraperitoneal transplantation of BM cells in a dynamic experiment. The level of peripheral T-helpers (CD4+) and Tregs (CD4+CD25+FOXP3+), and the expression of FOXP3 in the spleen and mesenteric lymph nodes were assessed. The material was collected on the 3rd and 21st days of the experiment. Results. Glycodelin was shown to reduce the absolute number of T-helpers in the peripheral blood (on the 3rd and 21st days) and to increase the proportion of Tregs on the 21st day of the experiment against the background of the introduction of allogeneic BM cells. It was found out, that glycodelin reduced the level of Tregs in the white pulp of the spleen on the 3rd day of the experiment, while the number of these cells on the 21st day increased, reducing the number of T-helpers at the same time. At the level of the mesenteric lymph nodes, glycodelin reduced the level of T-helpers on the 21st day of the experiment, simultaneously increasing the number of Tregs. In general, a unidirectional and distributed effect of glycodelin on the immune response at the level of T-helpers was observed, that was a decrease of T-helpers, but an increase of Tregs on the 21st day of the experiment. Conclusion. Thus, glycodelin had an immunomodulatory effect on T-helpers and Tregs formation. The vector of the obtained effects was immunosuppressive in nature and contributed to the suppression of the immune response to allogeneic cells.

Autoantibodies targeting interferons and GM-CSF are associated with adverse outcome risk, comorbidities, and pathogen in community-acquired pneumonia.

Cytokine autoantibodies (c-aAb) have been associated with pulmonary diseases, including severe novel coronavirus disease 2019 (COVID-19) and pulmonary alveolar proteinosis. This study aimed to determine c-aAb association with community-acquired pneumonia (CAP) etiology (SARS-CoV-2, influenza, or bacteria) and c-aAb associations with CAP-related clinical outcomes and pulmonary comorbidities. In a cohort of 665 patients hospitalized with CAP, c-aAb targeting interferon α (IFNα), IFNβ, IFNγ, interleukin-1α (IL-1α), IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in plasma samples. Associations between c-aAb and baseline characteristics, pulmonary comorbidities, pathogen, intensive care unit (ICU) transferal, time to clinical stability, and mortality were estimated, with results stratified by sex. More men infected with SARS-CoV-2 were had high-titer type 1 IFN c-aAb compared to other pathogens. Among patients with CAP, asthma and bronchiectasis comorbidities were associated with high-titer GM-CSF c-aAb in men, and men with high-titer IFNβ c-aAb had increased odds for ICU transferal. High-titer IL-10 c-aAb were associated with faster clinical stability in women. In men with CAP, various c-aAb-including type 1 IFN and GM-CSF c-aAb-were associated with adverse clinical events and comorbidities, whereas c-aAb targeting an autoinflammatory cytokine were associated with a positive outcome in women. This suggests that the potentially immunomodulatory effects of c-aAb depend on pathogen, autoantibody specificity, comorbidity, and sex.

The Antiviral Effects of Heat-Killed Lactococcus lactis Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway.

The growing risk of contracting viral infections due to high-density populations and ecological disruptions, such as climate change and increased population mobility, has highlighted the necessity for effective antiviral treatment and preventive measures against Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, there has been increasing attention on the use of probiotics as a potential antiviral option to reduce virus infections. The present study aimed to assess the immunomodulatory effects of heat-killed Lactococcus lactis strain plasma (LC-Plasma) on peripheral blood mononuclear cells (PBMCs) and its subsequent antiviral response against DENV, CHIKV, and ZIKV. To evaluate the immunomodulatory effects of LC-Plasma on PBMCs isolated from healthy individuals, PBMCs were cultured at a density of 2 × 105 cells/well and stimulated with 10 µg/mL of LC-Plasma. LC-plasma-stimulated PBMCs demonstrated elevated interferon-alpha (IFN-α) production and cluster of differentiation 86 (CD86) and human leukocyte antigen-DR isotype (HLA-DR) upregulation, potentially linked to plasmacytoid dendritic cell (pDC) activation. The replication of DENV, CHIKV, and ZIKV was dose-dependently inhibited when Huh-7 cells were stimulated with LC-Plasma-stimulated PBMC supernatant (LCP Sup). IFN-stimulated gene (ISG) expression, including IFN-stimulated gene 15 (ISG15), IFN-stimulated exonuclease gene 20 (ISG20), IFN-induced transmembrane protein 1 (IFITM-1), myxovirus resistance protein A (MxA), and radical S-adenosyl methionine domain-containing protein 2 (RSAD2), was significantly upregulated in LCP Sup-stimulated Huh-7 cells. Findings from this study indicate that LC-Plasma has the potential to induce IFN-α production, leading to an enhancement in the expression of ISGs and contributing to a broad-spectrum antiviral response. Thus, LC-Plasma may serve as a rational adjunctive treatment to ameliorate viral diseases, warranting future clinical trials.

Growth, immunomodulatory, histopathological, and antibacterial effects of phytobiotic-incorporated diets on Oreochromis niloticus in unchanged water

Phytobiotics are promising diet alternatives, yet their effectiveness in high-risk aquaculture conditions remains underexplored. Therefore, a 90-day feeding trial was conducted based on dietary supplementation of Nile tilapia, Oreochromis niloticus, with herbal extracts, namely, lemon balm [Melissa officinalis (MOE)], marjoram [Origanum majorana (OME)], and chamomile [Matricaria chamomilla (MCE)] with 0% water change. The treated groups were compared to groups untreated with herbs or control groups [positive control (PC; 0% water change) and negative control (NC; 20% water exchange per day]. Fish were cultured at stocking density (20 fish m-3: 1.8kg of biomass/m3). We conducted a physicochemical analysis of the water and the clinical responses, growth, and immune responses of the fish were evaluated. Furthermore, the herbal-supplemented fish were then challenged with a pathogenic Edwardseilla tarda strain and mortality was monitored. In the 1st and 2nd months, the water parameters were within the permissible limits. After that, a fatally low dissolved oxygen concentration and the highest levels of ammonia, nitrite, nitrate, and pH were recorded during the 3rd month. Blood and immune assays were conducted in the treated groups and control groups. The herbal-treated groups appeared healthy, but during the 3rd month, lethargy and decreased appetite were evident. Generally, the herbal-treated fish showed improved growth performance parameters, survival rates, and resistance against pathogenic bacteria E. tarda, particularly in the OME and MOE-treated groups compared to the positive control group. Finally, phytobiotic supplements were shown to improve fish stress tolerance and immune activation for a certain period under stressful conditions or unchanged water, based on the stocking density, dosages of herbs used, and the extent of deterioration of the water quality.

Influence of breastfeeding on the ontogenesis of mucosal immunity in children

The role of breastfeeding in the development of the cellular immune system, antimicrobial strategies of neutrophils, and local cytokine levels was evaluated in a single-center, prospective, open-label, uncontrolled study of healthy infants who were either naturally or artificially breastfed. The main group included practically healthy children who were exclusively breastfed for the first year of life. Thirty-six children were examined during the first stage and 25 from this group during the second stage. The comparison group included children who received an adapted cow’s milk formula during the first half-year of their lives and a different formula during the second half-year. Thirty-one children were examined during stage one and 27 from this group were examined during stage two. A comprehensive study of mucosal immunity was conducted, assessing the cytokine profile and cellular components using the method of smear prints from the nasal mucosa. The results showed that the nature of feeding during the first year of life influences the formation of mucosal immunity and programming the postnatal development of the child’s immunological reactivity. In the absence of the immunomodulatory effects of breast milk, there is an imbalance in the cytokine profile, with a physiological deviation of the immune response linked to the predominance of Th2 profiles. In contrast, breastfeeding promotes the optimal cellular composition of the upper respiratory mucosa and a cytomorphological neutrophil profile with minimal destructive changes. Breastfeeding programs the optimal functional profile of neutrophils, including the level of receptor activity, intracellular biocidal activity, cytotoxicity, ability to complete phagocytosis. This natural infant feeding method has a long-term protective effect, preventing neutrophil destruction under the influence of environmental factors and respiratory viral agents, and ensuring optimal mucosal immunity development in the respiratory tract.

Effects of Nigella sativa on disease activity, T lymphocytes and inflammatory cytokine profiles in pediatric systemic lupus erythematosus: A randomized controlled trial

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, requiring long-term treatment that can have side effects, particularly in pediatric patients. Nigella sativa (NS) has shown potential for improving SLE symptoms due to its anti-inflammatory and immunomodulatory effects. The aim of this study was to investigate the immunomodulatory effect of N. sativa oil (NSO) on disease activity, T lymphocyte activity and inflammatory cytokine profiles in pediatric SLE patients. A randomized, double-blinded, placebo-controlled clinical trial was conducted at Saiful Anwar Hospital in Malang, Indonesia, from January 2022 to January 2023. Pediatric patients with SLE were randomly assigned to receive either one gram of NSO or a placebo containing starch in capsule form as adjunct therapy alongside their SLE primary treatment. Blood samples were collected before treatment and after eight weeks of daily capsules. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K); flow cytometry was used to identify T helper lymphocytes, and serum cytokine levels were measured using ELISA. The statistical analysis tests were performed to compare the outcomes between groups at baseline or after the treatment, and within-group comparisons before and after the study period, as appropriate. A total of 32 patients were included in the study. A significant decrease in the SLEDAI-2K score was observed at post-treatment in both the NSO and placebo groups (p<0.001 and p=0.025, respectively). The percentage of T helper 17 (Th17) cells was significantly reduced in both the NSO and placebo groups post-treatment compared to pre-treatment (p=0.026 and p=0.034, respectively). Conversely, the post-treatment percentage of regulatory T (Treg) cells increased significantly in both groups. A significant reduction in interleukin (IL)-2 levels was observed in the NSO and placebo groups at post-treatment compared to pre-treatment (p=0.006 and p=0.046, respectively). Additionally, there were increases in IL-4 and IL-6 serum levels in both groups at post-treatment compared to pre-treatment (p<0.05). This study highlights that although disease activity was not significantly different between NSO and placebo groups, NSO could affect the inflammatory cytokine profiles in pediatric SLE patients.

Renoprotective Effects of Brown-Strain Flammulina velutipes Singer in Chronic Kidney Disease-Induced Mice Through Modulation of Oxidative Stress and Inflammation and Regulation of Renal Transporters.

Cisplatin, widely used in chemotherapy, acts through mechanisms such as oxidative stress to damage the DNA and cause the apoptosis of cancer cells. Although effective, cisplatin treatment is associated with considerable side effects including chronic kidney disease (CKD). Studies on brown-strain Flammulina velutipes Singer (FVB) have shown its significant antioxidant and immunomodulatory effects. High-performance liquid chromatography (HPLC) confirmed that the FVB extract contained gallic acid and quercetin. This study investigated whether FVB extract can improve and protect against cisplatin-induced CKD in mice. C57BL/6 mice were used as an animal model, and CKD was induced through intraperitoneal cisplatin injection. FVB was orally administered to the mice for 14 consecutive days. N-acetylcysteine (NAC) was administered in the positive control group. Organ pathology and serum biochemical analyses were conducted after the mice were sacrificed. Significant dose-dependent differences were discovered in body mass, kidney mass, histopathology, renal function, inflammatory factors, and antioxidant functions among the different groups. FVB extract reduced the severity of cisplatin-induced CKD in pathways related to inflammation, autophagy, apoptosis, fibrosis, oxidative stress, and organic ion transport proteins; FVB extract, thus, displays protective physiological activity in kidney cells. Additionally, orally administered high doses of the FVB extract resulted in significantly superior renal function, inflammatory factors, antioxidative activity, and fibrotic pathways. This study establishes a strategy for future clinical adjunctive therapy using edible-mushroom-derived FVB extract to protect kidney function.