Inhibition of 3-phosphoinositide-dependent protein kinase 1 (PDK1) can revert cellular senescence in human dermal fibroblasts.

Cellular senescence is defined as a stable, persistent arrest of cell proliferation. Here, we examine whether senescent cells can lose senescence hallmarks and reenter a reversible state of cell-cycle arrest (quiescence). We constructed a molecular regulatory network of cellular senescence based on previous experimental evidence. To infer the regulatory logic of the network, we performed phosphoprotein array experiments with normal human dermal fibroblasts and used the data to optimize the regulatory relationships between molecules with an evolutionary algorithm. From ensemble analysis of network models, we identified 3-phosphoinositide-dependent protein kinase 1 (PDK1) as a promising target for inhibitors to convert the senescent state to the quiescent state. We showed that inhibition of PDK1 in senescent human dermal fibroblasts eradicates senescence hallmarks and restores entry into the cell cycle by suppressing both nuclear factor κB and mTOR signaling, resulting in restored skin regeneration capacity. Our findings provide insight into a potential therapeutic strategy to treat age-related diseases associated with the accumulation of senescent cells.

The natural phytochemical trans-communic acid inhibits cellular senescence and pigmentation through FoxO3a activation.

Ageing is characterized by the accumulation of chronic and irreversible oxidative damage, chronic inflammation and organ dysfunction. To attenuate these ageing-related changes, various natural phytochemicals are often applied. Trans-communic acid (TCA), an active component of brown pine leaf extract, has antimicrobial and cancer chemopreventive activity and inhibits ultraviolet B (UVB)-induced MMP-1 expression. To determine whether the phytochemical TCA could affect the lifespan of an ageing model, Caenorhabditis elegans prevent ageing-related phenotypes of the skin. Caenorhabditis elegans (C. elegans) wild-type N2 and mutant strains were used in this study to explore the lifespan extension effect of TCA and its mechanism. We estimated lipofuscin accumulation and melanin levels, which are closely associated with skin senescence. Moreover, we explored the mechanism of action associated with ageing attenuation. We performed oxidative stress resistance and thermotolerance assays in C. elegans and surface plasmon resonance analysis of TCA binding with the forkhead box-O3a (FoxO3a) protein. TCA, which is the active component in Korean red pine (Pinus densiflora), attenuated ageing-related changes in skin cells. TCA lowered lipofuscin accumulation in fibroblasts and decreased melanin levels in melanocytes. These protective effects were mediated by activation of the representative longevity gene FoxO3a, which was induced by direct binding with TCA. Interestingly, TCA extended the lifespan of C. elegans, although it did not affect stress resistance, oxidative stress or thermotolerance. These results strongly suggest that TCA prevents the senescent phenotype of model organisms and exhibits beneficial effects on ageing-related skin phenotypes through direct FoxO3a activation.

Enantioselective induction of SIRT1 gene by syringaresinol from Panax ginseng berry and Acanthopanax senticosus Harms stem.

Syringaresinol exists either exclusively as one enantiomer or enantiomeric mixtures in plant foods. We found that (+)-syringaresinol, but not (-)-syringaresinol, upregulates silent information regulator two ortholog 1 (SIRT1) gene expression, and thus, Panax ginseng berry with predominantly high contents of (+)-syringaresinol exhibits higher activity in inducing SIRT1 gene expression than Acanthopanax senticosus Harms stem with almost equal proportion of the two enantiomers. These findings highlight the importance of the absolute configuration of syringaresinol for the biological activity.

Transcriptional activation of melanocortin 2 receptor accessory protein by PPARγ in adipocytes.

Adrenocorticotropic hormone (ACTH) in rodents decreases lipid accumulation and body weight. Melanocortin receptor 2 (MC2R) and MC2R accessory protein (MRAP) are specific receptors for ACTH in adipocytes. Peroxisome proliferator-activated receptor γ (PPARγ) plays a role in the transcriptional regulation of metabolic pathways such as adipogenesis and ß-oxidation of fatty acids. In this study we investigated the transcriptional regulation of MRAP expression during differentiation of 3T3-L1 cells. Stimulation with ACTH affected lipolysis in murine mature adipocytes via MRAP. Putative peroxisome proliferator response element (PPRE) was identified in the MRAP promoter region. In chromatin immunoprecipitation and reporter assays, we observed binding of PPARγ to the MRAP promoter. The mutagenesis experiments showed that the -1209/-1198 region of the MRAP promoter could function as a PPRE site. These results suggest that PPARγ is required for transcriptional activation of the MRAP gene during adipogenesis, which contributes to understanding of the molecular mechanism of lipolysis in adipocytes.

Acute effects of (-)-gallocatechin gallate-rich green tea extract on the cerebral hemodynamic response of the prefrontal cortex in healthy humans.

Objective: The benefits of long-term consumption of green tea on the brain are well known. However, among many ingredients of green tea, the acute effects of (-)-gallocatechin gallate-rich green tea extract (GCG-GTE), have received comparatively less attention. Herein, we investigated the acute effects of oral ingestion of green tea with GCG-GTE, which contains close replicas of the ingredients of hot green tea, on task-dependent hemodynamics in the prefrontal cortex of healthy adult human brains. Methods: In this randomized, double-blind, placebo-controlled, parallel group trial, 35 healthy adults completed computerized cognitive tasks that demand activation of the prefrontal cortex at baseline and 1 h after consumption of placebo and 900 mg of GCG-GTE extract supplement. During cognitive testing, hemodynamic responses (change in HbO2 concentration) in the prefrontal cortex were assessed using functional near-infrared spectroscopy (fNIRS). Results: In fNIRS data, significant group x session interactions were found in the left (p = 0.035) and right (p = 0.036) dorsolateral prefrontal cortex (DLPFC). In behavioral data, despite the numerical increase in the GCG-GTE group and the numerical decrease in the Placebo group, no significant differences were observed in the cognitive performance measure between the groups. Conclusion: The result suggests a single dose of orally administered GCG-GTE can reduce DLPFC activation in healthy humans even with increased task demand. GCG-GTE is a promising functional material that can affect neural efficiency to lower mental workload during cognitively demanding tasks. However, further studies are needed to verify this.

ß-endorphin suppresses ultraviolet B irradiation-induced epidermal barrier damage by regulating inflammation-dependent mTORC1 signaling.

Solar ultraviolet B (UVB) radiation triggers excessive inflammation, disrupting the epidermal barrier, and can eventually cause skin cancer. A previous study reported that under UVB irradiation, epidermal keratinocytes synthesize the proopiomelanocortin-derived peptide ß-endorphin, which is known for its analgesic effect. However, little is known about the role of ß-endorphin in UVB-exposed skin. Therefore, in this study, we aimed to explore the protective role of ß-endorphin against UVB irradiation-induced damage to the skin barrier in normal human keratinocytes (NHKs) and on a human skin equivalent model. Treatment with ß-endorphin reduced inflammatory responses in UVB-irradiated NHKs by inactivating the NF-κB signaling pathway. Additionally, we found that ß-endorphin treatment reversed UVB-induced abnormal epidermal proliferation and differentiation in NHKs and, thus, repaired the skin barrier in UVB-treated skin equivalents. The observed effects of ß-endorphin on UVB-irradiated NHKs were mediated via blockade of the Akt/mTOR signaling pathway. These results reveal that ß-endorphin might be useful against UVB-induced skin injury, including the disruption of the skin barrier function.

Kaempferol tetrasaccharides restore skin atrophy via PDK1 inhibition in human skin cells and tissues: Bench and clinical studies.

Skin aging is a major risk factor for the dermal diseases, and interventions to attenuate cellular senescence are expected to reduce the risk for age-related diseases involving skin atrophy. However, blocking cell death or extending proliferation causally results in side effects and an increased cancer risk. For identification of a safer approach, we focused on PDK1 inhibition, which could revert cellular senescence and reduce senescence factors in skin in vitro, in a human skin equivalent model and in an exploratory, placebo-controlled, interventional trial. Natural phytochemical kaempferol tetrasaccharides resulted in a significant reduction in cellular senescence, and an increase in collagen fiber was observed in the skin cell and human skin equivalent. Clinical enhancement in skin appearance was noted in multiple participants, and an immunohistochemical study revealed improvement in the histological appearance of skin tissue and extracellular matrix. This change was associated with relative improvement in histological markers of senescence and clinical appearance of the aged skin and an increase in collagen fiber, an essential factor for preventing skin atrophy and consistency of the basement membrane. These results indicate that PDK1 inhibition is a potentially effective antiaging intervention, suggesting a diagnostic role and preventive actions of PDK1 in senescence-associated skin atrophy.

Curcumin attenuates oxidative stress and inflammatory response in the early phase after partial hepatectomy with simultaneous intraabdominal infection in rats.

BACKGROUND: Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections. MATERIAL AND METHODS: Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-alpha, IL-6 mRNA, and quantification of IL-1beta by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state. RESULTS: After simultaneous PH+CLP curcumin significantly reduced the expression of TNF-alpha and IL-6 mRNA in the liver tissue. The IL-1beta concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14+/-3%) than in the untreated PH+CLP group (7%+/-3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group. CONCLUSION: In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

Effects of chitooligosaccharide lactate salt on sleep deprivation-induced fatigue in mice.

Chitooligosaccharides (COS), oligosaccharides composed of two to seven glucosamine residues, are known to exhibit various biological activities. In this study, we investigated the effects of COS in an in vivo mouse sleep deprivation-induced fatigue model in an effort to develop a functional food with anti-fatigue efficacy. Male Balb/c mice were orally administered 500 mg (kg d)(-1) of COS lactate or COS HCl for 2 weeks, and severe fatigue was induced by sleep deprivation. To evaluate the extent of fatigue, the swimming time, representing the immobility time, was measured in a forced swim test. As a result, oral intake of COS lactate-manifested anti-fatigue effects could be observed by the attenuation of fatigue-induced body weight loss and shorter immobility period. In addition, COS lactate was shown to alleviate the fatigue-induced increase in cortisol and lipid peroxidation and a decrease in superoxide dismutase (SOD) activity. Of particular note, the oral administration of COS lactate increased the mitochondrial membrane potential and the mitochondrial number significantly, indicating that COS lactate may enhance mitochondrial function. In support of this, COS lactate increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and cytochrome c (Cyt C) mRNA, indicating that it may increase mitochondrial biogenesis. These results suggest that COS lactate can be an effective anti-fatigue functional food, and this anti-fatigue effect may result from, at least in part, the enhancement of mitochondrial biogenesis and the inhibition of free radical generation.

EEG Revealed That Fragrances Positively Affect Menopausal Symptoms in Mid-life Women.

During mid-life, women experienced not only physical but also neurological transition. Because of this, many women suffer from physiological and/or psychological menopausal symptoms. Although hormone therapy (HT) was broadly used to alleviate menopausal symptoms, HT showed inconsistent effects in case of psychological symptoms. Moreover, mid-life women's brains have distinct characteristics than in other periods of life, it is needed to study psychological symptoms in shifted brain network of mid-life women. As an alternative, inhalation of fragrances may alleviate psychological menopausal symptoms. To characterize the alleviation mechanism by fragrances, we tested the effect of fragrances on menopausal symptoms using electroencephalographic (EEG) methods. We hypothesized that fragrance could restore mid-life women's brain response to stressful situations. We tested six fragrance conditions, including no-odor condition (solvent only) in twenty-eight mid-life women (49.75 years±3.49). Our results showed that fragrances increased alpha power and decreased ß/α ratio depending on the severity of menopausal symptoms in a stressful situation. Our study would be helpful in psychological menopausal symptom alleviation as well as fragrance screening for well-being in mid-life.

Proteomic analysis of mitochondrial proteins of basal and lipolytically (isoproterenol and TNF-alpha)-stimulated adipocytes.

The regulation of adipocyte lipolysis is increasingly believed to influence insulin resistance, in a process that may be associated with mitochondrial dysfunction. However, the molecular basis of the relationship between mitochondrial protein expression, lipolytic responsiveness, and insulin resistance remains unknown. A set of proteins that shows altered abundances in the mitochondria of untreated and treated 3T3-L1 adipocytes with TNF-alpha or isoproterenol was identified. These include the proteins associated with energy production, including fatty acid oxidation, TCA cycle, and oxidative phosphorylation. Proteins associated with oxidative stress dissipation were down-regulated in lipolytically stimulated adipocytes. Lipolytic stimulation with isoproterenol and TNF-alpha, which is also a potent proinflammatory cytokine, showed some noticeable differences in mitochondrial protein expression. For example, isoproterenol markedly enhanced the expression of prohibitin which is involved in the integrity of mitochondria but TNF-alpha did not. These results provide valuable information on mitochondrial dysfunction associated with oxidative stress induced by lipolytic stimulation.

Transcriptional activation of Cidec by PPARgamma2 in adipocyte.

Cidec is a lipid droplet-associated protein, which inhibits lipolysis, leading to the accumulation of triglycerides in adipocytes. However, the transcriptional regulation of Cidec in adipocyte remains unknown. In the present study we investigated that the mouse Cidec transcript is regulated by PPARgamma2. After the differentiation of adipocyte, the expression pattern of Cidec was similar to that of PPARgamma2. In the presence of a PPARgamma agonist, the level of Cidec mRNA was highly increased. In addition, putative PPRE sites were identified in the Cidec promoter. By chromatin immunoprecipitation assay and reporter assay, we observed the binding of PPARgamma2 to the promoter of Cidec. Gel shift assay and the mutagenesis study were showed that the -219/-207 region of the Cidec promoter could function as a PPRE of the Cidec promoter. These results suggest that PPARgamma2 is required for the transcriptional activity of Cidec during adipogenesis, which could be contributed to understand the molecular mechanism of lipid droplet formation in adipocytes.

Catechin gallates are NADP+-competitive inhibitors of glucose-6-phosphate dehydrogenase and other enzymes that employ NADP+ as a coenzyme.

Recent studies have shown that glucose-6-phosphate dehydrogenase (G6PD) is an effectual therapeutic target for metabolic disorders, including obesity and diabetes. In this study, we used in silico and conventional screening approaches to identify putative inhibitors of G6PD and found that gallated catechins (EGCG, GCG, ECG, CG), but not ungallated catechins (ECG, GC, EC, C), were NADP(+)-competitive inhibitors of G6PD and other enzymes that employ NADP(+) as a coenzyme, such as IDH and 6PGD.

Synergistic effect of erythropoietin but not G-CSF in combination with curcumin on impaired liver regeneration in rats.

INTRODUCTION: The effect of erythropoietin (Epo) and granulocyte colony-stimulating factor (G-CSF) alone or in combination with the hepatoprotective antioxidant curcumin (Cur) was evaluated in a model of delayed liver regeneration. MATERIALS AND METHODS: Sprague Dawley rats underwent 70% liver resection with simultaneous cecal ligation and puncture and were randomised to five groups: no treatment, G-CSF (100 microg/kg), Epo (1,000 IU/kg), each alone or in combination with Cur (100mg/kg). Twenty-four hours after surgery, blood and tissue samples were collected. Markers of liver regeneration (liver weight, mitotic index, Ki-67 index), function (bilirubin, bile flow) and hepatocellular damage (liver enzymes, histomorphology) were determined. In addition, cytokine expression and hepatic glutathione concentrations were measured. RESULTS: Liver regeneration was not improved by G-CSF or Epo monotherapy. Epo more effectively increased liver weight and regeneration markers, but the difference was not significant. Whereas liver regeneration was slightly inhibited in the G-CSF plus Cur group, Epo plus Cur significantly improved liver regeneration. This was accompanied by reduced oxidative stress. Liver function and the expression of pro-inflammatory cytokines were comparable in all treatment groups. CONCLUSION: In the present model, Epo, at a relatively low dosage, did not improve liver regeneration. However, the combination of Epo and Cur showed a synergistic effect with highly significant stimulation of liver regeneration.

The effects of BADGE and caffeine on the time-course response of adiponectin and lipid oxidative enzymes in high fat diet-fed C57BL/6J mice: correlation with reduced adiposity and steatosis.

Adiponectin, which is expressed exclusively in adipose tissue, has been shown to increase fatty acid oxidation via activation of AMP-activated kinase (AMPK) and phosphorylation of acetyl CoA carboxylase (ACC). ACC phosphorylation and carnitine palmitoyl-transferase-1 (CPT1) activity have been shown to be rate controlling factors in fatty acid oxidation. In high fat diet (HFD)-induced obese mice, we analyzed the time-course of changes in the expression of adiponectin and lipid oxidative enzymes induced by treatment with bisphenol A diglycidyl ether (BADGE) or caffeine for 8 weeks, and investigated whether the changes of adiponectin and lipid oxidative enzymes expression correlated with reduced adiposity or steatosis after 8 weeks of treatment. After 8 weeks of treatment, BADGE and caffeine had reduced body weight and epididymal adipose tissue weight in mice fed HFD, and markedly reduced the number of fatty droplets in the liver. Interestingly, the expression of adiponectin and lipid oxidative enzymes significantly increased after 2 weeks of treatment. These results indicate that the expression of adiponectin and lipid oxidative enzymes in the early stages of BADGE or caffeine treatment correlated well with the long-term anti-obesity effects.

Identification of the domains required for the localization of Prp19p to lipid droplets or the nucleus.

Prp19p is a protein found in the nucleus, cytosol or lipid droplets depending on the cell type. Prp19p participates in pre-mRNA splicing, in neuronal/astroglial cell fate decisions or in adipocyte lipid droplet biogenesis. In this study, the motifs of Prp19p that are necessary for its localization to lipid droplets or the nucleus in 3T3-L1 adipocytes are investigated using a series of truncated mutants of Prp19p that were fused to EGFP and transiently introduced into differentiated 3T3-L1 adipocytes. Immunofluorescence microscopy revealed that a domain of amino acids 167-250 is necessary for the recruitment of Prp19p to lipid droplets and that a domain of amino acids 1-166 is necessary for the recruitment of Prp19p to a nucleus.

Effects of Korean ginseng berry on skin antipigmentation and antiaging via FoxO3a activation.

BACKGROUND: The ginseng berry has various bioactivities, including antidiabetic, anticancer, antiinflammatory, and antioxidative properties. Moreover, we have revealed that the active antiaging component of the ginseng berry, syringaresinol, has the ability to stimulate longevity via gene activation. Despite the many known beneficial effects of ginseng, its effects on skin aging are poorly understood. In this study, we investigated the effects of ginseng and the ginseng berry on one of the skin aging processes, melanogenesis, and age-related pigment lipofuscin accumulation, to elucidate the mechanism of action with respect to antiaging. METHODS: The human melanoma MNT1 cell line was treated with ginseng root extract, ginseng berry extract, or syringaresinol. Then, the cells were analyzed using a melanin assay, and the tyrosinase activity was estimated. The Caenorhabditis elegans wild type N2 strain was used for the life span assay to analyze the antiaging effects of the samples. A lipofuscin fluorescence assay was performed during 10 passages with the syringaresinol treatment. RESULTS: A 7-d treatment with ginseng berry extract reduced melanin accumulation and tyrosinase activity more than ginseng root extract. These results may be due to the active compound of the ginseng berry, syringaresinol. The antimelanogenic activity was strongly coordinated with the activation of the longevity gene foxo3a. Moreover, the ginseng berry extract had more potent antiaging effects, caused a life span extension, and reduced lipofuscin accumulation. CONCLUSION: Taken together, our results suggest that these antimelanogenic effects and antiaging effects of ginseng berry mediate the activation of antioxidation-FoxO3a signaling.

Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis.

This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103(-)CD11c⁺ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103⁺CD11c⁺ cDCs and expansion of Foxp3⁺ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis.

Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice.

Age-associated immunological dysfunction (immunosenescence) is closely linked to perturbation of the gut microbiota. Here, we investigated whether syringaresinol (SYR), a polyphenolic lignan, modulates immune aging and the gut microbiota associated with this effect in middle-aged mice. Compared with age-matched control mice, SYR treatment delayed immunosenescence by enhancing the numbers of total CD3+ T cells and naïve T cells. SYR treatment induced the expression of Bim as well as activation of FOXO3 in Foxp3+ regulatory T cells (Tregs). Furthermore, SYR treatment significantly enhanced the Firmicutes/Bacteroidetes ratio compared with that in age-matched controls by increasing beneficial bacteria, Lactobacillus and Bifidobacterium, while reducing the opportunistic pathogenic genus, Akkermansia. In addition, SYR treatment reduced the serum level of lipopolysaccharide-binding protein, an inflammatory marker, and enhanced humoral immunity against influenza vaccination to the level of young control mice. Taken together, these findings suggest that SYR may rejuvenate the immune system through modulation of gut integrity and microbiota diversity as well as composition in middle-aged mice, which may delay the immunosenescence associated with aging.

Ginseng Berry Extract Promotes Maturation of Mouse Dendritic Cells.

Ginseng extract has been shown to possess certain anti-virus, anti-tumor and immune-activating effects. However, the immunostimulatory effect of ginseng berry extract (GB) has been less well characterized. In this study, we investigated the effect of GB on the activation of mouse dendritic cells (DCs) in vitro and in vivo. GB treatment induced up-regulation of co-stimulatory molecules in bone marrow-derived DCs (BMDCs). Interestingly, GB induced a higher degree of co-stimulatory molecule up-regulation than ginseng root extract (GR) at the same concentrations. Moreover, in vivo administration of GB promoted up-regulation of CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in spleen DCs. GB also promoted the generation of Th1 and Tc1 cells. Furthermore, Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) signaling pathway were essential for DC activation induced by GB. In addition, GB strongly prompted the proliferation of ovalbumin (OVA)-specific CD4 and CD8 T cells. Finally, GB induced DC activation in tumor-bearing mice and the combination of OVA and GB treatment inhibited B16-OVA tumor cell growth in C57BL/6 mice. These results demonstrate that GB is a novel tumor therapeutic vaccine adjuvant by promoting DC and T cell activation.