[Preparation and in vitro evaluation of rhein-loaded PEG-PCL-PEI nanoparticles].

This study was aimed to synthesize the polyethyleneglycol-polycaprolactone-polyethyleneimine (PEG-PCL-PEI) three block polymer material, prepareRhein (RH)-loaded PEG-PCL-PEI nanoparticles(PPP-RH-NPS), and then evaluate their physical and chemical properties and biological characteristics in vitro. PEG-PCL-PEI polymer was obtained by adopting thering-opening polymerization and Michael addition reaction, and their physical and chemical properties were analyzed by using NMR and gel permeation chromatography. PEG-PCL-PEI was then used as the carriers to prepare PPP-RH-NPS by applying spontaneous emulsification solvent diffusion method. The results showed that molecular weight of PEG-PCL-PEI polymer was 9.5×103, and critical micelle concentration was 0.723 mmol•L⁻¹. PPP-RH-NPS had pale yellow, opalescence faade, round and smooth without aggregation, formed of (118.3±3.6) nm in particle size with PDI of (0.19±0.08), Zeta potential of (6.3±1.5) mV, entrapment efficiency of (93.64±5.28)%, and drug loading of (8.57±0.53)%. The accumulative release percentage of PPP-RH-NPS was 75.92% in 48h, and the release profiles in PBS conformed to the Higuchi equation： Q=0.121 6t1/2+0.069 5 (R²=0.887 4), presenting slow release characteristics. Within the scope of the 0-0.05 mmol•L⁻¹, the nanoparticles had no obvious hemolysis on rabbit red blood cells and toxicity on HK-2 cells. In the investigation of uptake efficiency by flow cytometry, nanoparticles can be absorbed into cells quickly and internalized within 30 minutes fully, with a high uptake efficiency. In confocal laser scanning microscope observation, the nanoparticles can escape from lysosome into cytoplasm. Herein, this study synthesized the PEG-PCL-PEI polymer and prepared PPP-RH-NPS successfully; the nanoparticles showed uniform particle size, higher encapsulation efficiency and drug-loading rate, slow release characteristics, quick uptake and internalization, lysosome escape property and good biocompatibility. PPP-RH-NPS will be a promising pharmaceutical formulation for further development.

ERP Study of Affirmative and Negative Sentences' Impact on Self-Positivity Bias.

To explore how the sentence contexts affect self-positivity bias, we presented the participants with negation and affirmation sentences. Each sentence was ended with an adjective word describing human being's personality. The participants were asked to judge whether the sentences correctly described their own personalities. In affirmation sentences, the behavioral data showed that self-positivity bias occurred when participants considered the sentences to be in accordance with their personality; the ERP data showed that P200 amplitude was consistent with this behavioral result. In negation sentences, behavioral data showed self-positivity bias, regardless of whether the sentences were in accordance with participants' personality or not. However, the self-positivity bias was not observed in the ERP results from negation sentence. In summary, sentence type modulated the effect of self-positivity bias. The reason could be that processing affirmation and negation sentences requires different amount of cognitive resources.

Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study.

Context: Despite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD. Methods: By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy. Results: After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10-5, PFDR =0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10-5, PFDR =0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10-4, PFDR =0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It's worth noting that 20 phenotypes exist where ADHD's appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (ß= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (ß= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (ß=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (ß= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (ß=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (ß= -0.255, 95% CI: 0.621~0.967, P=0.234), among others. Conclusion: Studies indicate that the immune system's response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.

Effects of 5-HT on the cold resistance of mangrove Kandelia obovata seedlings.

5-hydroxytryptamine (5-HT) participates in plant growth and development, and can also delay senescence and cope with abiotic stress. To explore the role of 5-HT in regulating the abilities of mangrove in cold resis-tance, we examined the effects of cold acclimation and the spraying of p-chlorophenylalanine (p-CPA, 5-HT synthesis inhibitor) on leaf gas exchange parameters and CO2 response curves (A/Ca), as well as the endogenous phytohormone content levels in the mangrove species Kandelia obovata seedlings under low temperature stress. The results showed that low temperature stress significantly reduced the contents of 5-HT, chlorophyll, endogenous auxin (IAA), gibberellin (GA), and abscisic acid (ABA). It weakened the CO2 utilization abilities of plants and reduced net photosynthetic rate, which ultimately reduced carboxylation efficiency (CE). Under low temperature stress, exogenous p-CPA reduced the contents of photosynthetic pigments, endogenous hormones, and 5-HT in the leaves, which aggravated the damages caused by low temperature stress on photosynthesis. By enhancing cold acclimation abilities, the endogenous IAA content in the leaves could was reduced under low temperature stress, promoted the production of 5-HT, improved the contents of photosynthetic pigments, GA, and ABA, as well as enhanced photosynthetic carbon assimilation abilities, which would increase photosynthesis in the K. obovata seedlings. Under cold acclimation conditions, the spraying of p-CPA could significantly inhibit the synthesis of 5-HT, promote the production of IAA, and reduce the contents of photosynthetic pigments, GA, ABA, and CE, which would weaken the effects of cold acclimation by improving the cold resistance of mangroves. In conclusion, cold acclimation could improve the cold resistance abilities of K. obovata seedlings by regulating photosynthetic carbon assimilation capacity and the contents of endogenous phytohormone. 5-HT synthesis is one of the necessary conditions for improving the cold resistance abilities of mangroves.

A bidirectional Mendelian randomization study about the role of morning plasma cortisol in attention deficit hyperactivity disorder.

Context: Cortisol, a hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, has been linked to attention deficit hyperactivity disorder (ADHD). The nature of the relationship between cortisol and ADHD, and whether it is causal or explained by reverse causality, remains a matter of debate. Objective: This study aims to evaluate the bidirectional causal relationship between morning plasma cortisol levels and ADHD. Methods: This study used a bidirectional 2-sample Mendelian randomization (MR) design to analyze the association between morning plasma cortisol levels and ADHD using genetic information from the authoritative Psychiatric Genomics Collaboration (PGC) database (n = 55,347) and the ADHD Working Group of the CORtisol NETwork (CORNET) Consortium (n = 12,597). MR analyses were employed: inverse variance weighting (IVW), MR-Egger regression, and weighted medians. OR values and 95% CI were used to evaluate whether there was a causal association between morning plasma cortisol levels on ADHD and ADHD on morning plasma cortisol levels. The Egger-intercept method was employed to test for level pleiotropy. Sensitivity analysis was performed using the "leave-one-out" method, MR pleiotropy residual sum, and MR pleiotropy residual sum and outlier (MR-PRESSO). Results: Findings from bidirectional MR demonstrated that lower morning plasma cortisol levels were associated with ADHD (ADHD-cortisol OR = 0.857; 95% CI, 0.755-0.974; P = 0.018), suggesting there is a reverse causal relationship between cortisol and ADHD. However, morning plasma cortisol levels were not found to have a causal effect on the risk of ADHD (OR = 1.006; 95% CI, 0.909-1.113; P = 0.907), despite the lack of genetic evidence. The MR-Egger method revealed intercepts close to zero, indicating that the selected instrumental variables had no horizontal multiplicity. The "leave-one-out" sensitivity analysis revealed stable results, with no instrumental variables significantly affecting the results. Heterogeneity tests were insignificant, and MR-PRESSO did not detect any significant outliers. The selected single-nucleotide polymorphisms (SNPs) F were all >10, indicating no weak instrumental variables. Thus, the overall MR analysis results were reliable. Conclusion: The study findings suggest a reverse causal relationship between morning plasma cortisol levels and ADHD, with low cortisol levels associated with ADHD. No genetic evidence was found to support a causal relationship between morning plasma cortisol levels and the risk of ADHD. These results suggest that ADHD may lead to a significant reduction in morning plasma cortisol secretion.

Antimicrobial activity of saponin-rich fraction from Camellia oleifera cake and its effect on cell viability of mouse macrophage RAW 264.7.

BACKGROUND: As a by-product of oil production, several million tons of Camellia oleifera cake is discarded every year in China. The aim of this study was to evaluate the antimicrobial activity of a saponin-rich fraction isolated from C. oleifera cake and investigate its effect on the cell viability of RAW 264.7, a macrophage-like cell line present in almost all mouse tissues. RESULTS: The saponin-rich fraction was isolated from C. oleifera cake in several steps and had a saponin content of 95.42 ± 0.10% (w/w). It showed significant inhibitory activity against the bacteria Staphylococcus aureus, Escherichia coli and Bacillus subtilis and the fungi Mucor racemosus, Aspergillus oryzae, Rhizopus stolonifer, Saccharomyces cerevisiae and Penicillium glaucum, with minimum inhibitory concentrations of 31.3, 31.3, 62.5, 250, 250, 250, 31.3 and 125 µg ml(-1) respectively. In addition, mouse macrophage RAW 264.7 pretreated with the saponin-rich fraction (80-200 µg mL(-1) ) exhibited a significant loss of cell viability in a dose-dependent manner. CONCLUSION: These results may be useful for the future application of saponins from C. oleifera cake. However, the potential use of the saponin-rich fraction as an antimicrobial agent should be decided according to the target micro-organisms in order to avoid causing harm in humans.

Age-Related Sex Disparities in Esophageal Cancer Survival: A Population-Based Study in the United States.

Background: The association between sex and the survival of patients with esophageal cancer (EC) remains controversial. We sought to systematically investigate sex-based disparities in EC survival using the Surveillance, Epidemiology, and End Results (SEER) registry data from the United States. Methods: Patients with EC diagnosed from 2004 to 2015 registered in the SEER database were selected. The association between sex and cancer-specific survival (CSS) was evaluated using survival analysis. The Inverse Probability Weighting (IPW) approach was applied to reduce the observed bias between males and females. Subgroup analyses were used to investigate the robustness of the sex-based disparity and to explore potential interaction effects with other variables. Results: Overall, 29,312 eligible EC patients were analyzed, of whom 5,781 were females, and 23,531 were males. Females had higher crude CSS compared to males (10-year CSS: 24.5 vs. 21.3%; P < 0.001). Similar results were obtained after adjusting for selection bias using the IPW approach and multivariate regression. Subgroup analyses confirmed the relative robustness of sex as a prognostic factor. However, significant interactions were observed between sex and other variables, such as age, race, tumor grade, histology, and treatment modality. In particular, there was no survival advantage for premenopausal females compared to their male counterparts, but the association between sex and EC survival was prominent in 46-55-year-old patients. Conclusions: Female EC patients had better long-term survival than males. The association between sex and EC survival vary according to age, race, tumor grade, histology, and treatment modality. Sex-based disparity in EC-specific survival was age-related in the United States population.

Benefit of chemotherapy in stage III nasopharyngeal carcinoma: Analysis of the surveillance, epidemiology, and end results database.

OBJECTIVES: Chemoradiotherapy is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). We aimed to reveal factors associated with chemotherapy use and evaluate chemotherapy's benefit in patients with stage III NPC stratified by lymph node status. PATIENTS AND METHODS: Overall, 1452 patients with stage III NPC who underwent radiotherapy with (n = 1361) or without (n = 91) chemotherapy were identified in the SEER database. We examined predictors for chemotherapy use using logistic regression analysis. We compared all-cause mortality (ACM) and cancer-specific mortality (CSM) using the Kaplan-Meier method. Cox regression and competing risk analyses were used to evaluate the benefit of chemotherapy. The inverse probability of treatment weighting (IPTW) approach was applied to reduce selection bias and adjust for competing risks. Subgroup analyses and interaction effects were explored. RESULTS: Factors including age, sex, insured status, tumor grade, and N category were associated with chemotherapy use. Chemotherapy was associated with decreased 5-year ACM (31.4% vs. 48.4%, p < 0.001) and CSM (25.5% vs. 35.8%; p = 0.017) in stage III NPC patients. The IPTW-adjusted hazard ratio for 5-year ACM was 0.57 (95% CI: 0.38-0.86, p = 0.008), whereas IPTW-adjusted sub-hazard ratio for 5-year CSM was 0.62 (95% CI: 0.42-0.93, p = 0.003). A significant interaction effect existed between lymph node status and treatment modality. Chemotherapy offered a significant survival benefit in node-positive stage III NPC. However, no chemotherapy benefit for the node-negative disease was observed. CONCLUSION: Chemotherapy adds survival benefit in stage III NPC, especially in patients with node-positive disease. The magnitude of chemotherapy benefit in node-negative stage III NPC warrants further investigation.

Structural elucidation of four new furostanol saponins from Tupistra chinensis by 1D and 2D NMR spectroscopy.

Four new furostanol saponins (1-4), two pairs of diastereoisomers, were isolated from methanolic extracts of Tupistra chinensis rhizomes and their structures were assigned from (1)H and (13)C NMR spectra, DEPT, and by 2D COSY, NOESY, HMQC, and HMBC experiments.

Invasive-noninvasive Sequential Ventilation for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: The study aimed to evaluate the efficacy and safety of invasivenoninvasive sequential ventilation versus invasive ventilation in the treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). METHODS: PubMed, Cochrane, Embase, Wanfang, CNKI, VIP database were searched by the index words to identify the qualified RCTs, and relevant literature sources were also searched. The latest research was conducted in June 2017. Relative Risks (RR), and Mean Difference (MD) along with 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULTS: Twenty-nine RCTs were involved in this analysis of 1061 patients in the invasivenoninvasive sequential ventilation group (In-non group) and 1074 patients in the invasive ventilation group (In group). The results indicated that compared with the invasive ventilation, invasive-noninvasive sequential ventilation would significantly decrease the incidence of VAP (RR:0.20, 95%CI: 0.16-0.26), mortality (RR:0.38, 95%CI: 0.26-0.55), reintubation (RR:0.39, 95%CI: 0.27-0.55); and statistically reduced the duration of invasive ventilation (MD:-9.23, 95%CI: -10.65, -7.82), the total duration of mechanical ventilation (MD:-4.91, 95%CI: -5.99, -3.83), and the length of stay in the ICU (MD:-5.10, 95%CI: -5.43, -4.76). CONCLUSION: The results demonstrated that the application of noninvasive sequential ventilation after invasive ventilation at the pulmonary infection control window has a significant influence on VAP incidence, mortality, and the length of stay in the ICU, but further well-designed, adequately powered RCTs are required to validate the conclusion.

[Chemical constituents of antibacterial activity fraction of Angelica polymorpha].

OBJECTIVE: To study chemical constituents of antibacterial activity fraction of Angelica polymorpha. METHODS: Compounds were isolated by repeatedly silica gel column chromatography and recrystallization. Their structures were identified by physical and chemical evidences and spectral methods. RESULTS: Seven compounds were obtained from the antibacterial activity fraction, their structures were elucidated as: bisabolangelone(I), isoimperatorin (II), oxypeucedanine(III), isooxypeucedanine(IV), oxypeucedanin hydrate(V), bergapten(VI), pabulenol(VII). CONCLUSION: Bisabolangelone(I) is obtained from this plant for the first time. Compound (II)-(VII) belong to linear furanocourmarins.

SlMYB12 Regulates Flavonol Synthesis in Three Different Cherry Tomato Varieties.

Cherry tomato (Lycopersicon esculentum M.) is considered a healthy fruit worldwide due to its wide range of nutrients. Flavonol, one of the major nutrients in cherry tomato, has antioxidant and cell-modulating properties. In this study, we showed a correlation between the expression of SlMYB12 and flavonol content (R2 = 0.922). To characterize the function of SlMYB12, SlMYB12-overexpressing transgenic tomato plants were generated in three different cherry tomato varieties. Significant increases in flavonol content and flavonol biosynthetic gene expression were identified in SlMYB12-overexpressing plants. Therefore, we suggest that SlMYB12 plays a positive role in the flavonol biosynthesis pathway in cherry tomatoes, which further indicates a potential role as a marker in analyzing flavonol content in different cherry tomato varieties.

Effect of Lactobacillus plantarum NCU116 Fermentation on Asparagus officinalis Polysaccharide: Characterization, Antioxidative, and Immunoregulatory Activities.

Lactic acid fermentation represents a novel method to produce bioactive functional ingredients, including polysaccharides. In this work, a selected lactic acid bacteria strain NCU116 was used to ferment Asparagus officinalis (asparagus) pulps. Two polysaccharides were subsequently separated from both unprocessed and fermented asparagus pulps, namely, asparagus polysaccharide (AOP) and fermented-AOP (F-AOP). The physicochemical and bioactive properties of AOP and F-AOP were characterized and investigated. High-performance anion-exchange chromatography showed that fermentation increased the proportions of rhamnose, galacturonic acid, and glucuronic acid in polysaccharides by 46.70, 114.09, and 12.75‰, respectively. High-performance size-exclusion chromatography revealed that fermentation decreased the average molecular weight from 181.3 kDa (AOP) to 152.8 kDa (F-AOP). Moreover, the fermentation reduced the particle size and changed the rheology property. In vitro, F-AOP displayed superior free radical scavenging properties compared to AOP, using 2,2-diphenyl-1-picryhydrazyl, hydroxyl, and superoxide anion radical scavenging assays. In vivo, F-AOP administration dose-dependently promoted a gradual shift from Th17-dominant acute inflammatory response (IL-17 and RORγt) to Th1-dominant defensive immune response (IFN-γ and T-bet). These results indicated that the Lactobacillus plantarum NCU116 fermentation was practical and useful to obtain promising bioactive polysaccharides.

New polyhydroxylated furostanol saponins with inhibitory action against NO production from Tupistra chinensis rhizomes.

Two furostanol saponins were obtained from the rhizomes of Tupistra chinensis Bak. Their structures were determined as 5beta-furost-delta(25(27))-en-1beta,2beta,3beta,4beta,5beta,7alpha,22xi,26-octaol-6-one-26-O-beta-D-glucopyranoside (1) and 5beta-furost-delta(25(27))-en-1beta,2beta,3beta,4beta,5beta,6beta,7alpha,22xi,26-nonaol-26-O-beta-D-glucopyranoside (2), on the basis of chemical and spectroscopic evidence. Both compounds displayed marked inhibitory action against NO production in rat abdomen macrophages induced by lipopolysaccharide (LPS) at 40 microg/mL.

Circulating 25-hydroxyvitamin D level and prognosis of lung cancer patients: A systematic review and meta-analysis.

BACKGROUND: Previous studies suggested a possible influence of circulating 25-hydroxyvitamin D [25(OH)D] level on the prognosis of lung cancer patients, but conflicting findings were reported. A systematic review and meta-analysis was thus conducted to comprehensively assess the influence of circulating 25(OH)D level on the prognosis of lung cancer patients. METHODS: Prospective or retrospective cohort studies assessing the influence of circulating 25(OH)D level on the prognosis of lung cancer patients were considered eligible. Hazard Ratios (HR) were pooled using meta-analysis. RESULTS: Eight studies with 2166 lung cancer patients were included. Meta-analysis of unadjusted HRs from four studies showed low circulating 25(OH)D level was significantly correlated with poor overall survival in lung cancer (HR=1.30, 95%CI 1.08-1.55, P=0.004). Meta-analysis of adjusted HRs from eight studies suggested that low circulating 25(OH)D level was not significantly correlated with poor overall survival (HR=1.25; P=0.13). However, sensitivity analysis suggested an obvious change in the pooled HRs when excluding single study by turns. When the study by Liu et al. was omitted, low circulating 25(OH)D level was significantly correlated with poor overall survival (HR=1.34; P=0.04). CONCLUSION: The present systematic review and meta-analysis suggested a correlation between low circulating 25(OH)D level and poor overall survival in lung cancer. More studies are needed to further validate the finding above.

Subclass opioid receptors associated with the cardiovascular depression after traumatic shock and the antishock effects of its specific receptor antagonists.

The present available opioid receptor antagonists such as naloxone and naltrexone are not highly receptor selective. They may antagonize mu opioid receptors to affect the pain threshold of the patients with traumatic shock while they exert antishock effects. Therefore, they are not suitable for traumatic shock. It is very important to elucidate the subclass of opioid receptors that are closely associated with cardiovascular depression of traumatic shock and then choose their specific receptor antagonists to treat it. Traumatic shock was used in pentobarbital-anesthetized Wistar rats by right femur fracture plus hemorrhage (fixed hemorrhage at a rate of 20 mL/kg in experiment 1 or hemorrhage to 40 mmHg mean arterial blood pressure for 60 min in experiments 2 and 3), and the changes of myocardial and brain opioid receptors after traumatic shock, the antagonizing effects of mu, delta, and kappa opioid receptor antagonists on the cardiovascular depression of traumatic shock and the antishock effects of delta and kappa opioid receptor antagonists ICI174,864 and Nor-binaltorphimine (Nor-BNI) were observed. The results indicate that after traumatic shock, the number of myocardial and brain delta and kappa opioid receptors were significantly increased that were significantly associated with the decreased cardiovascular functions. mu Opioid receptors in the heart and brain did not change significantly. Intracerebral ventricular administration of ICI174,864 and Nor-BNI significantly antagonized the decreased cardiovascular function after traumatic shock and increased the survival rate of traumatic shock rats, but mu opioid receptor antagonist beta-funaltrexamine did not. Meanwhile, intravenous administration of delta and kappa opioid receptor antagonists ICI174,864 and Nor-BNI also significantly increased the mean arterial blood pressure, improved the hemodynamic parameters, and prolonged the survival rate of traumatic shock rats. These findings suggest that opioid receptors are involved in the cardiovascular depression of traumatic shock, and the subclass receptors are mainly delta and kappa opioid receptors. delta and kappa opioid receptor antagonists have good beneficial effects on traumatic shock.

Toll-like receptor 4 mediates the antitumor host response induced by Ganoderma atrum polysaccharide.

The aim of this study is to investigate the role of Toll-like receptor (TLR) 4 in Ganoderma atrum polysaccharide (PSG-1)-induced antitumor activity. In vitro, the apoptosis rate of S-180 cells was increased in PSG-1-induced peritoneal macrophage derived from C3H/HeN (wild-type) mice, but not from C3H/HeJ (TLR4-deficient) mice. In the S-180 tumor model, phagocytosis, NO and ROS release, phosphorylation of MAPKs and Akt, and expression of NF-κB were increased by PSG-1 in peritoneal macrophage derived from C3H/HeN mice. Furthermore, PSG-1 elevated Th1 cytokine production and enhanced the cytotoxic activity of CTL and NK cells in C3H/HeN mice. In addition, PSG-1 decreased the tumor weight and increased the apoptosis rate and caspase-3 and caspase-9 activities of tumor derived from the C3H/HeN mice. However, none of these activities were observed in C3H/HeJ mice. In summary, these findings demonstrated that the antitumor activity of PSG-1 is mediated by TLR4.

Signaling pathway involved in the immunomodulatory effect of Ganoderma atrum polysaccharide in spleen lymphocytes.

The aim of this study was to investigate the molecular mechanism underlying the immunomodulatory effect of Ganoderma atrum polysaccharide (PSG-1) in spleen lymphocytes. Our results showed that PSG-1 increased the intracellular Ca2+ concentration and calcineurin (CaN) activity. Moreover, PSG-1 was found to elevate nuclear factor of activated T cells (NFAT) activity, but this effect could be diminished by the treatment of CaN inhibitors (cyclosporin A and FK506). PSG-1-induced interleukin (IL)-2 production was also inhibited by cyclosporin A and FK506. In addition, PSG-1 was found to significantly enhance protein kinase C (PKC) activity. PKC was involved in induction of NFAT activity by PSG-1, as evidenced by abrogation of NFAT activity by PKC inhibitor calphostin C, which significantly decreased PSG-1-induced IL-2 production. On the basis of these results, we concluded that PSG-1 may induce activation of spleen lymphocytes at least in part via the Ca2+/CaN/NFAT/IL-2 signaling pathway and the PKC/NFAT/IL-2 signaling pathway cooperatively regulated PSG-1-induced activation of spleen lymphocytes.

Carboxymethylation enhances the maturation-inducing activity in dendritic cells of polysaccharide from the seeds of Plantago asiatica L.

Carboxymethylation is a well-known modification process for polysaccharides. To evaluate the biological availability of carboxymethyl, polysaccharide from the seeds of Plantago asiatica L. (PLCP) was carboxymethylated (CM-PLCP) and the immunomodulatory activities of five CM-PLCPs of gradient degree of substitution (DS) from 0.40 to 0.62 were determined on dendritic cells (DCs) in vitro. Compared with DCs treated with PLCP, DCs treated with CM-PLCP of DS0.50, DS0.55, DS0.62, as well as CD86 and CD80, expressed higher levels of MHCII, CD86 and CD80 surface molecules. In addition, the secretion of IL-12p70 and the mRNA of CCR7 and CXCR4 chemokines were increased, while the endocytosis activities were inhibited. Correspondingly, stronger mixed lymphocyte reactions were induced by the DCs treated with the CM-PLCPs. The results showed that carboxymethylation modification of relevant high DS can enhance the DC maturation-inducing function of PLCP, indicating the potential application of carboxymethylated polysaccharide as an immunotherapeutic adjuvant.