Immune-enhancing neutrophils reprogrammed by subclinical low-dose endotoxin in cancer treatment.

Despite the re-emergence of the pioneering "Coley's toxin" concept in anti-cancer immune therapies highlighted by check-point inhibitors and CAR-T approaches, fundamental mechanisms responsible for the immune-enhancing efficacy of low-dose "Coley's toxin" remain poorly understood. This study examines the novel reprogramming of immune-enhancing neutrophils by super-low dose endotoxin conducive for anti-cancer therapies. Through integrated analyses including scRNAseq and functional characterizations, we examined the efficacy of reprogrammed neutrophils in treating experimental cancer. We observed that neutrophils trained by super-low dose endotoxin adopt a potent immune-enhancing phenotype characterized by CD177loCD11bloCD80hiCD40hiDectin2hi. Both murine and human neutrophils trained by super-low dose endotoxin exhibit relieved suppression of adaptive T cells as compared to un-trained neutrophils. Functionally, neutrophils trained by super-low dose endotoxin can potently reduce tumor burden when transfused into recipient tumor-bearing mice. Mechanistically, Super-low dose endotoxin enables the generation of immune-enhancing neutrophils through activating STAT5 and reducing innate suppressor IRAK-M. Together, our data clarify the long-held mystery of "Coley's toxin" in rejuvenating anti-tumor immune defense, and provide a proof-of-concept in developing innate neutrophil-based anti-tumor therapeutics.

Nasally delivered chitosan-coated poly(lactide-co-glycolide) encapsulating honeybee venom enhances T helper 1-related immunity against Salmonella Typhimurium infection in pigs.

OBJECTIVE: Salmonella Typhimurium is a significant zoonotic concern for human food poisoning and a substantial economic burden in the swine industry. We previously reported that nasally delivered chitosan-coated poly(lactide-co-glycolide) (PLGA) encapsulating honeybee venom (CP-HBV) could enhance CD4+ T helper 1 (Th1)-related immune responses in healthy pigs. Building upon these findings, the current study aimed to investigate the protective immune enhancement by nasally delivered CP-HBV in pigs challenged with S Typhimurium. ANIMALS: 36 healthy, 4-week-old, female, Landrace X Yorkshire X Duroc pigs. METHODS: 36 pigs were allocated into 3 groups: CP-HBV (n = 16), control (n = 16), and healthy baseline control (n = 4). CP-HBV and control groups were challenged with S Typhimurium 7 days post-treatment. Pigs from the healthy control group were sacrificed at 0 days postinfection (DPI), and 4 pigs from each of the control and CP-HBV groups were sacrificed at 1, 2, 4, and 7 DPI. Salmonella shedding, immune cell frequencies, cytokines, and transcriptional factor expression levels were measured. RESULTS: The CP-HBV group exhibited lower bacterial shedding and an enhanced Th1-related immune response characterized by an upregulation of CD4+ T cells and CD4+ Interferon-γ+ T cells, accompanied by increased expression of Th1-related cytokines and reduced expression of regulatory T cells and immunosuppressive cytokines compared to the control group. CLINICAL RELEVANCE: CP-HBV is a promising strategy for controlling Salmonella infections in pigs and improving public health.

Early prediction and prevention of infected pancreatic necrosis.

Approximately 20%-30% of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis (IPN), a highly morbid and potentially lethal complication. Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes. In the past two decades, several markers and predictive tools have been proposed and evaluated for this purpose. Conventional biomarkers like C-reactive protein, procalcitonin, lymphocyte count, interleukin-6, and interleukin-8, and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN. On the other hand, scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested, and the results showed that they may provide better accuracy. For early prevention of IPN, several new therapies were tested, including early enteral nutrition, antibiotics, probiotics, immune enhancement, etc., but the results varied. Taken together, several evidence-supported predictive markers and scoring systems are readily available for predicting IPN. However, effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition. In this editorial, we summarize evidence concerning early prediction and prevention of IPN, providing insights into future practice and study design. A more homogeneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN, thereby achieving individualized treatment.

Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice.

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy.

Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression.

The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and the resulting immunosuppressive microenvironment, leading to the chronicity and recurrence of IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO2@Ce6@Van (BMCV). The BMCV exhibits precise targeting and adhesion to the S. aureus biofilm-infected region, coupled with its capacity to catalyze oxygen generation from H2O2 in the hypoxic and acidic biofilm microenvironment (BME), promoting oxygen-dependent photodynamic therapy efficacy while ensuring continuous release of manganese ions. Notably, targeted BMCV can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting the biofilm structure and impairing its barrier function, making it vulnerable to infiltration and elimination by the immune system. Furthermore, light-induced reactive oxygen species (ROS) around the biofilm can lyse S. aureus, triggering bacterium-like immunogenic cell death (ICD), releasing abundant immune costimulatory factors, facilitating the recognition and maturation of antigen-presenting cells (APCs), and activating adaptive immunity. Additionally, manganese ions in the BME act as immunoadjuvants, further amplifying macrophage-mediated innate and adaptive immune responses and reversing the immunologically cold BME to an immunologically hot BME. We prove that our synthesized BMCV elicits a robust adaptive immune response in vivo, effectively clearing primary IAIs and inducing long-term immune memory to prevent recurrence. Our study introduces a potent light-induced immunomodulatory nanoplatform capable of reversing the biofilm-induced immunosuppressive microenvironment and disrupting biofilm-mediated protective barriers, offering a promising immunotherapeutic strategy for addressing challenging S. aureus IAIs.

Innate Immune-Enhancing Effect of Pinus densiflora Pollen Extract via NF-κB Pathway Activation.

Considering the emergence of various infectious diseases, including the coronavirus disease 2019 (COVID-19), people's attention has shifted towards immune health. Consequently, immune-enhancing functional foods have been increasingly consumed. Hence, developing new immune-enhancing functional food products is needed. Pinus densiflora pollen can be collected from the male red pine tree, which is commonly found in Korea. P. densiflora pollen extract (PDE), obtained by water extraction, contained polyphenols (216.29 ± 0.22 mg GAE/100 g) and flavonoids (35.14 ± 0.04 mg CE/100 g). PDE significantly increased the production of nitric oxide (NO) and reactive oxygen species (ROS) but, did not exhibit cytotoxicity in RAW 264.7 cells. Western blot results indicated that PDE induced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. PDE also significantly increased the mRNA and protein levels of cytokines and the phosphorylation of IKKα/ß and p65, as well as the activation and degradation of IκBα. Additionally, western blot analysis of cytosolic and nuclear fractions and immunofluorescence assay confirmed that the translocation of p65 to the nucleus after PDE treatment. These results confirmed that PDE increases the production of cytokines, NO, and ROS by activating NF-κB. Therefore, PDE is a promising nutraceutical candidate for immune-enhancing functional foods.

The Potential of Korean Bioactive Substances and Functional Foods for Immune Enhancement.

In this review, we explore the immunomodulatory properties of Korean foods, focusing on ginseng and fermented foods. One notable example is Korean red ginseng, known for its immune system-regulating effects attributed to the active ingredient, ginsenoside. Ginsenoside stimulates immune cells, enhancing immune function and suppressing inflammatory responses. With a long history, Korean red ginseng has demonstrated therapeutic effects against various diseases. Additionally, Korean fermented foods like kimchi, doenjang, chongkukjang, gochujang, vinegar, and jangajji provide diverse nutrients and bioactive substances, contributing to immune system enhancement. Moreover, traditional Korean natural herbs such as Cirsium setidens Nakai, Gomchwi, Beak-Jak-Yak, etc. possess immune-boosting properties and are used in various Korean foods. By incorporating these foods into one's diet, one can strengthen their immune system, positively impacting their overall health and well-being.

Shape-Regulated Photothermal-Catalytic Tumor Therapy Using Polydopamine@Pt Nanozymes with the Elicitation of an Immune Response.

Recently, nanozyme-based photothermal-catalytic therapy has emerged as a promising strategy for antitumor treatment. Extensive research has focused on optimizing the catalytic activity and photothermal conversion performance of nanozymes through size, morphology, and surface property regulations. However, the biological effects of nanozymes, such as cellular uptake and cytotoxicity, resulting from their physicochemical properties, remain largely unexplored. In this study, two types of polydopamine/platinum (PDA@Pt) nanozymes, flower-like (FPDA@Pt) and mesoporous spherical-like (MPDA@Pt), to comprehensively compare their enzyme-mimicking activity, photothermal conversion capacity, and antitumor efficiency are designed. These findings revealed that FPDA@Pt exhibited superior peroxidase-like activity and higher photothermal conversion efficiency compared to MPDA@Pt. This led to enhanced production of reactive oxygen species (ROS) and increased heat generation at tumor sites. Importantly, it is observed thatthe flower-like structure of FPDA@Pt facilitated enhanced cellular uptake, leading to an increased accumulation of nanozymes within tumor cells. Furthermore, the light irradiation on tumors also triggered a series of anti-tumor immune responses, further enhancing the therapeutic efficacy. This work provides a possible design orientation for nanozyme-based photothermal-catalytic tumor therapy, highlighting the importance of considering the physicochemical properties of nanozymes to optimize their therapeutic potential in antitumor strategies.

MDA5 with Complete CARD2 Region Inhibits the Early Replication of H9N2 AIV and Enhances the Immune Response during Vaccination.

Chicken melanoma differentiation-associated gene 5 (MDA5) is a member of the RLRs family that recognizes the viral RNAs invading cells and activates downstream interferon regulatory pathways, thereby inhibiting viral replication. The caspase activation and recruitment domain (CARD) is the most important region in MDA5 protein. However, the antiviral and immune enhancement of MDA5 with the CARD region remains unclear. In this study, two truncated MDA5 genes with different CARD regions, namely MDA5-1 with CARD1 plus partial CARD2 domain and MDA5-2 with CARD1 plus complete CARD2 domain, were cloned via reverse transcription PCR and ligated into plasmid Flag-N vector to be Flag-MDA5-1 and Flag-MDA5-2 plasmids. DF-1 cells were transfected with two plasmids for 24 h and then inoculated with H9N2 virus (0.1 MOI) for 6 h to detect the levels of IFN-ß, PKR, MAVS, and viral HA, NA, and NS proteins expression. The results showed that MDA5-1 and MDA5-2 increased the expression of IFN-ß and PKR, activated the downstream molecule MAVS production, and inhibited the expression of HA, NA, and NS proteins. The knockdown of MDA5 genes confirmed that MDA5-2 had a stronger antiviral effect than that of MDA5-1. Furthermore, the recombinant proteins MDA5-1 and MDA5-2 were combined with H9N2 inactivated vaccine to immunize SPF chickens subcutaneously injected in the neck three times. The immune response of the immunized chicken was investigated. It was observed that the antibody titers and expressions of immune-related molecules from the chicken immunized with MDA5-1 and MDA5-2 group were increased, in which the inducing function of MDA5-2 groups was the highest among all immunization groups. These results suggested that the truncated MDA5 recombinant proteins with complete CARD2 region could play vital roles in antiviral and immune enhancement. This study provides important material for the further study of the immunoregulatory function and clinical applications of MDA5 protein.

Permafrost viremia and immune tweening.

The immune system, an exquisitely regulated physiological system, utilizes a wide spectrum of soluble factors and multiple cell populations and subpopulations at diverse states of maturation to monitor and protect the organism against foreign organisms. Immune surveillance is ensured by distinguishing self-antigens from self-associated with non-self (e.g., viral) peptides presented by major histocompatibility complexes (MHC). Pathology is often identified as unregulated inflammatory responses (e.g., cytokine storm), or recognizing self as a non-self entity (i.e., auto-immunity). Artificial intelligence (AI), and in particular specific machine learning (ML) paradigms (e.g., Deep Learning [DL]) proffer powerful algorithms to better understand and more accurately predict immune responses, immune regulation and homeostasis, and immune reactivity to challenges (i.e., immune allostasis) by their intrinsic ability to interpret immune parameters, pathways and events by analyzing large amounts of complex data and drawing predictive inferences (i.e., immune tweening). We propose here that DL models play an increasingly significant role in better defining and characterizing immunological surveillance to ancient and novel virus species released by thawing permafrost.

Immune-Stimulating Potential of Lacticaseibacillus rhamnosus LM1019 in RAW 264.7 Cells and Immunosuppressed Mice Induced by Cyclophosphamide.

Probiotics, including Lacticaseibacillus rhamnosus (L. rhamnosus), have gained recognition for their potential health benefits, such as enhancing immune function, maintaining gut health, and improving nutrient absorption. This study investigated the effectiveness of L. rhamnosus LM1019 (LM1019) in enhancing immune function. In RAW 264.7 cells, LM1019 demonstrated dose-dependent immune stimulation by increasing nitric oxide production, gene expression of proinflammatory cytokines, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These effects were mediated through the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) translocation without inducing cytotoxicity. Furthermore, orally administered LM1019 was evaluated in immunosuppressed mice induced by cyclophosphamide (CTX). High-dose administration of LM1019 significantly increased the subpopulations of lymphocytes, specifically helper T cells (CD4+), as well as two subtypes of natural killer (NK) cells, namely, IFN-γ+ and granzyme B+ NK cells. Additionally, LM1019 at a high dose led to elevated levels of proinflammatory cytokines, including IFN-γ and IL-12, compared to CTX-treated mice. These findings highlight the potential of LM1019 in enhancing the immune system. The study contributes to the growing body of research on the beneficial effects of probiotics on immune function.

Anti-tumor activity of trimethoprim-sulfamethoxazole against melanoma skin cancer through triggering allergic reaction and promoting immunity.

The anti-cancer impact of an allergic reaction is strongly linked to immunity enhancement. Trimethoprim-sulfamethoxazole (TMP-SMX), an antibiotic, has potential immunomodulatory effects, but has side effects such as allergies. Thus far, the effects and underlying mechanisms of TMP-SMX in melanoma have not been clarified. This study examined the potential roles of TMP-SMX in melanoma skin cancer using an immunodeficient mouse model. TMP-SMX significantly improved the survival rate and reduced the tumor weight and growth and vascular endothelial growth factor levels in melanoma skin cancer of immunodeficient mice. In the forced swimming test, TMP-SMX significantly reduced immobility time compared to the melanoma skin cancer of immunodeficient mice, indicating improved immunity. TMP-SMX significantly increased infiltration of mast cells and release of allergy-related mediators (IgE, histamine, interleukin (IL)-4, IL-5, IL-13, and IL-33) and immune-enhancing mediators (tumor necrosis factor-α, IL-2, IL-6, and IL-12). In addition, the administration of TMP-SMX significantly increased the caspase-3, 8, and 9 activities. Furthermore, mice given TMP-SMX showed no adverse reactions according to the blood biochemical parameters. TMP-SMX significantly inhibits the growth of melanoma skin cancer by triggering an allergic reaction and promotingimmunity. Hence, we propose that TMP-SMX may be used as an immune booster in cancer chemotherapy.

Beta 1,3-1,6 Glucans Produced by Two Novel Strains of Aureobasidium Pullulans Exert Immune and Metabolic Beneficial Effects in Healthy Middle-aged Japanese Men: Results of an Exploratory Randomized Control Study.

Objectives: In this pilot study, we have evaluated the specific metabolic and immune-related benefits of the AFO-202 strain and N-163 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in healthy human subjects. Methods: Sixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta-glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta-glucan (2 sachets of 1 g each) and N-163 beta-glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days. Results: Decrease in HbA1C and glycated albumin (GA), significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I between pre- and post-treatment. Decrease in total and LDL cholesterol, a decrease of CD11b, serum ferritin, galectin-3 and fibrinogen were profound in Group II between pre- and post-treatment. However, there was no statistically significant difference between day 21 and day 35 among the groups. Conclusion: This outcome warrants larger clinical trials to explore the potentials of these safe food supplements in the prevention and prophylaxis of diseases due to dysregulated metabolism, such as fatty liver disease, and infections such as COVID-19 in which balanced immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases.

Immune-enhancement effects of Angelica gigas Nakai extracts via MAPK/NF-ƙB signaling pathways in cyclophosphamide-induced immunosuppressed mice.

This study investigated the immune-enhancement effects of Angelica gigas Nakai extract (ANE) and its yeast-fermented extract (FAN) in cyclophosphamide (CPP)-induced immunosuppressed mice. Angelica gigas Nakai (AGN) increased the protein level of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) and immune-related cytokines in mouse splenocytes. AGN also restored CPP-induced suppression of NK cell activity and splenocyte proliferation. Furthermore, AGN activated the ERK and p38 MAPK/NF-κB signaling pathways in mouse splenocytes via phosphorylation of signaling molecules. These findings indicate that upregulation of cytokines and enzymes may be closely associated with the MAPK/NF-κB signaling pathways. In conclusion, AGN can restore CPP-induced immunosuppression in mice, although there was no significant difference in the immune-enhancing effect between ANE and FAN. It is suggested that AGN might have the potential to enhance immunity as an immunostimulant under immunosuppressed conditions. Therefore, it could be used as an effective agent or a dietary supplement for improving immunity. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01281-6.

Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model.

Background: Euonymus alatus (Thunb.) Siebold (EA) is a medicinal plant used in some Asian countries to treat various diseases, including cancer, hyperglycemia, diabetes, urticaria, dysmenorrhea, and arthritis. Owing to the wide range of pharmacological applications of EA, various roles of EA are being studied. Objective: We evaluated the immune-enhancing effect of EA treatment in a cyclophosphamide (Cy)-induced immunosuppressed rat model. Design: We analyzed the immune enhancement effect of EA on macrophages by western blotting. In addition, cell viability and natural killer (NK) cell activity were analyzed in splenocytes following EA treatment. For in vivo studies, analysis of weekly body weight, spleen weight, immune cell count, cytokine levels, and spleen histological findings was performed following EA administration in Cy-induced immunocompromised rats. Results: EA significantly increased cell viability and phospho-nuclear factor-kappa B and phospho-extracellular signal-regulated kinase protein levels in the macrophages. EA significantly increased NK cell activity in splenocytes compared with the control group. In Cy-induced immunosuppressed rats, EA administration increased spleen tissue weight and the contents of leukocytes, lymphocytes, granulocytes, intermediate cells, and plasma cytokines (tumor necrosis factor-α and interferon-γ). In addition, improvement in the damaged spleen tissue was observed. Conclusions: These findings confirm that EA exerts an immune-enhancing effect, thereby suggesting its potential as an immunostimulatory agent or functional food.

Theabrownin Isolated from Pu-Erh Tea Enhances the Innate Immune and Anti-Inflammatory Effects of RAW264.7 Macrophages via the TLR2/4-Mediated Signaling Pathway.

Theabrownin (TB) is a tea pigment extracted from Pu-erh Tea. The effects of TB on innate immunity and inflammation are not well understood. Herein, the effects of TB on innate immunity are investigated using RAW264.7 macrophages. We found that TB promoted the proliferation of RAW264.7 macrophages, altered their morphology, enhanced their pinocytic and phagocytic ability, and significantly increased their secretion of nitric oxide (NO) and cytokines, all of which enhanced the immune response. Additionally, TB inhibited the release of inflammatory signals in RAW264.7 macrophages primed with lipopolysaccharide (LPS), implying that TB modulates the excessive inflammation induced by bacterial infection. A Western blot showed that TB could activate the toll-like receptor (TLR)2/4-mediated myeloid differentiation factor 88 (MyD88)-dependent mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathway and the TLR2-mediated phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, enhancing the immune functions of RAW264.7 macrophages. TB also inhibited the phosphorylation of core proteins in the MAPK/NF-κB/PI3K-AKT signaling pathway induced by LPS. In addition, we analyzed the transcriptomes of RAW264.7 macrophages, and a Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed that TB modulated thetoll-like receptor signal pathway. A gene ontology (GO) enrichment analysis indicated that TB treatment strongly modulated the immune response and inflammation. As a result, TB-enhanced innate immunity and modulated inflammation via the TLR2/4 signaling pathway.

Early Oral Administration of Ginseng Stem-Leaf Saponins Enhances the Peyer's Patch-Dependent Maternal IgA Antibody Response to a PEDV Inactivated Vaccine in Mice, with Gut Microbiota Involvement.

Neonatal piglets during the first week of life are highly susceptible to porcine epidemic diarrhoea virus (PEDV) infection, with mortality rates reaching 80-100%. Passive lactogenic immunity remains the most effective way to protect neonates from infection. Although safe, inactivated vaccines provide little or no passive protection. Here, we administered ginseng stem-leaf saponins (GSLS) to mice before parenteral immunization with an inactivated PEDV vaccine to investigate the effect of GSLS on the gut-mammary gland (MG)-secretory IgA axis. Early oral GSLS administration potently increased PEDV-specific IgA plasma cell generation in the intestine, facilitated intestinal IgA plasma cell migration to the MG by enhancing the chemokine receptor (CCR)10-chemokine ligand (CCL)28 interaction, and ultimately promoted specific IgA secretion into milk, which was dependent on Peyer's patches (PPs). Additionally, GSLS improved the gut microbiota composition, especially increasing probiotic abundance, and these microflora members promoted the GSLS-enhanced gut-MG-secretory IgA axis response and were regulated by PPs. In summary, our findings highlight the potential of GSLS as an oral adjuvant for PEDV-inactivated vaccines and provide an attractive vaccination strategy for lactogenic immunity induction in sows. Further studies are required to evaluate the mucosal immune enhancement efficacy of GSLS in pigs.

An arabinogalactan isolated from Pollen Typhae induces the apoptosis of RKO cells by promoting macrophage polarization.

An arabinogalactan (PTPS-1-2) was isolated and characterized from Pollen Typhae, and its potential antitumor effects on activating macrophages to produce immunomodulatory factors and promoting apoptosis in colorectal cancer cells were investigated. Structural characterization showed that PTPS-1-2 had a molecular weight of 59 kDa and was composed of rhamnose, arabinose, glucuronic acid, galactose, and galacturonic acid with a molar ratio of 7.6: 17.1: 6.5: 61.4: 7.4. Its backbone was predominantly composed of T-ß-D-Galp, 1,3-ß-D-Galp, 1,6-ß-D-Galp, 1,3,6-ß-D-Galp, 1,4-α-D-GalpA, 1,2-α-L-Rhap, additionally, branches contained 1,5-α-L-Araf, T-α-L-Araf, T-ß-D-4-OMe-GlcpA, T-ß-D-GlcpA and T-α-L-Rhap. PTPS-1-2 activated RAW264.7 cell by triggering the NF-kB signaling pathway and M1 macrophage polarization. Furthermore, the conditioned medium (CM) of Mφ pretreated with PTPS-1-2 exerted marked antitumor effects by inhibiting RKO cell proliferation and suppressing cell colony formation. Collectively, our findings suggested that PTPS-1-2 might be a therapeutic option for the prevention and treatment of tumors.

Selenium Nanoparticles Based on Morinda officinalis Polysaccharides: Characterization, Anti-Cancer Activities, and Immune-Enhancing Activities Evaluation In Vitro.

Recently, selenium nanoparticles have been drawing attention worldwide, and it is crucial to increase the stability of nano-Se. Morinda officinalis polysaccharides (MOP) are the main active component in Morinda officinalis radix. However, their low activity has limited their application. A novel selenium nanoparticle (Se-MOP) was prepared to solve these problems using MOP as a dispersant. The zeta potential was measured to evaluate the stability, and UV and ATR-FTIR were used to investigate the binding type of selenium and MOP. The morphology was observed by the TEM method. Furthermore, the inhibitory effect on five selected cancer cells (HepG2, MCF-7, AGS, PC9, and HCT8) was evaluated, showing remarkable inhibition of all five cancer cells. The mechanism of inhibition was also investigated by cell circle assay, and it was found that Se-MOP could induce cell circle G0/G1 phase arrest. Immune-enhancing activities were evaluated by measuring the proliferation and cytokines of mouse spleen lymphocytes in vitro and quantitative RT-PCR. The results indicated that single stimulation of Se-MOP and synergistic stimulation with PHA or LPS increased immune capacity and improved immune by increasing the expression of cytokines.