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Most patients are at high risk of thrombosis during cancer treatment. However, the major discrepancy in the therapeutic mechanisms and microenvironment between tumors and thrombosis makes it challenging for a panacea to treat cancer while being able to eliminate the risk of thrombosis. Herein, we developed a biomimetic MnOx/Ag more...

Intravesical instillation has been widely utilized for bladder cancer treatment in clinic. However, due to the bladder mucosal barrier, its poor penetration efficiency and drug utilization limit the clinical therapeutic effectiveness and result in a high recurrence rate. Therefore, designing an efficient and controllable drug delivery nanoplatform is of great significance for bladder cancer treatment. Non-invasive therapy based on near-infrared-II (NIR-II) photothermal therapy (PTT) conduces to overcome bladder mucosal barrier and enhance drug delivery. Also, the photothermal nanomaterials, Au Hollow Nanorods (AuHNRs), demonstrate strong photothermal properties and drug loading capacity. Herein, a quaternized chitosan more...

One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, we herein present the performance of selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy. By encapsulating coagulation-inducing protease thrombin and a hypoxia-activated prodrug (HAP) tirapazamine into metal-organic framework nanoparticles with a tumor-homing ligand, the obtained nanoplatform selectively activates the platelet aggregation at tumor to induce the thrombosis and vascular obstruction therapy by the exposed thrombin. Meanwhile, the thrombus can cut off the blood oxygen supply and potentiate the hypoxia levels to enhance the HAP therapy. This strategy not only addresses the dissatisfaction of vascular therapy, but also conquers the dilemma of inadequate hypoxia in the HAP treatment. Since clinical operations such as surgery can be used to induce the coagulation, the coagulation based synergistic therapy is promising to be translated into a clinical combination regimen. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Submitted/Accepted version This work was supported by grants from the National Natural Science Foundation of China (21778020, 31750110464, and 31950410755), the Sci-Tech Innovation Foundation of Huazhong Agricultural University (2662018PY024), the National Key R&D Program of China (2016YFD0500706), and the Science and Technology Major Project of Guangxi (Gui Ke AA18118046). This work was also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081), and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03). more...

Microcystin-LR (MCLR) induced impairment to male reproductive system and revealed the effects of transgenerational toxicity on offspring. But very little is known about the inheritance of these effects to offspring and the mechanisms involved. Here, we used methylated DNA immunoprecipitation sequencing (MeDIP-Seq) and microarray to characterize whole-genome DNA methylation and mRNA expression patterns in zebrafish testis after 6-week exposure to 5 and 20 μg/L MCLR. Accompanied with these analyses it revealed that MAPK pathway and ER pathway significantly enriched in zebrafish testes. Apoptosis and testicular damage were also observed in testis. Next, we test the transmission of effects to compare control-father and MCLR exposure-father progenies. DNA methylation analyses (via reduced representation bisulfite sequencing) reveal that the enrichment of differentially methylated regions on neurodevelopment after paternal MCLR exposure. Meanwhile, several genes associated with neurodevelopment were markedly downregulated in zebrafish larvae, and swimming speed was also reduced in the larvae. Interestingly, paternal MCLR exposure also triggered activation the phosphorylation of mitogen-activated protein kinase (MAPK) pathway which is also associated with neurodevelopmental disorders. These results demonstrated the significant effect that paternal MCLR exposure may have on gene-specific DNA methylation patterns in testis. Inherited epigenetic alterations through the germline may be the mechanism leading to developmental neurotoxicity in the offspring. more...

In order to investigate the effect of yeast on reducing mycotoxin damage in dried fish.A strain of Meyerozyma guilliermondii MH 211588. 1(MG-81) was mixed and fermented 48 h with dried Lutjanus erythopterus which contaminated aflatoxin B_1(AFB_1) and T-2 toxin(T-2). The toxin concentration in fermentation at different time was detected by LC-MS/MS, and fermentation was fed with mice by intragastric administration(7 d). Blood routine and four liver function enzymes were measured by hematology analyzer and microplate spectrophotometer respectively. The elimination effect of MG-81 isolate on mycotoxin damage in dried fish was evaluated by the toxin concentration at different time and its toxic effect on mice.The removal rates of AFB_1 and T-2 in dried fish fermentation showed a parabolic linear growth trend with the prolongation of fermentation time. The removal rates of AFB_1 and T-2 in dried fish fermentation broth tended to be stable at 36 h(the removal rates of AFB_1 and T-2 were 83. 7%±1. 3% and 78. 5%±0. 8%). This indicated that 36 h was the optimal time for MG-81 to remove mycotoxins in dried fish. At the same time, it was found that there was no significant change in the indexes of MG-81 dried fish fermentation compared with the control group(Pgt;0. 05), while the same dose of AFB_1 and T-2 dried fish fermentation(without MG-81), the leucocytes, lymphocytes, erythrocyte, hemoglobin, platelet and mean platelet volume of mice were significantly lower than those of control group(Pgt;0. 05), showing obvious hemotoxicity and immunotoxicity. The activity of four liver enzymes was increased significantly(Plt;0. 05), showing obvious hepatotoxicity.The fermentation of MG-81 for 36 h can effectively remove AFB_1 and T-2 from dried fish and eliminate their hazards. more...

Photothermal therapy (PTT) is considered an alternative for oncotherapy because it has less invasive damage to normal tissues than other methods, particularly in second near-infrared (NIR-II) PTT (1000-1350 nm) because of deeper biological tissue penetration, lower photon scattering, and higher maximum permissible exposure (1.0 W cm more...

Bacteria show promise for use in the field of combination cancer therapy because of their abilities to accumulate in tumors and their roles as natural immunologic adjuvants. However, the huge size of bacteria decreases their chances of being delivered into tumor cells. Moreover, their toxins may cause systemic toxicity in living organisms. Here, we proposed a method to in situ synthesize Au nanoparticles on the surface of Escherichia coli (E. coli), followed by sonication to acquire Au nanoparticles loaded membrane nanosheets (AuMNs) for use in photothermal and combination cancer therapy. Compared to E. coli-loaded Au nanoparticles (E. coli@Au), the small size of membrane nanosheets can be successfully delivered into tumor cells. In addition, the enrichment of AuMNs in tumor site is significantly enhanced via EPR effect, facilitating to activate photothermal conversion under 808 nm laser. Besides, the function of bacteria as natural immunologic adjuvants to promote anti-PD-L1 efficacy is still retained in AuMNs, while the inflammation and damage to viscera caused by AuMNs were milder than E. coli@Au. This study aims to decrease the systemic toxicity of bacteria and promote anti-PD-L1 efficacy in bacteria-mediated combination therapy, so as to open up a new avenue for drug delivery via natural processes. more...

The strategy that combines photodynamic therapy (PDT) and photothermal therapy (PTT) is widely used to achieve strong antitumor efficiency. Since light in the NIR-II window possesses ideal penetration ability, developing NIR-II PTT and NIR-II light triggered photosensitizer release for combined PDT and PTT is very promising in nanomedicine. Methods: We develop a novel nanocarrier (termed AuHNRs-DTPP) by conjugating photosensitizer contained chimeric peptide (DTPP) to Au hollow nanorods (AuHNRs). AuHNRs was obtained by a Te-templated method with the assistance of L-cysteine. The chimeric peptide PpIX-PEG8-GGK(TPP)GRDEVDGC (DTPP) was obtained through a solid-phase peptide synthesis (SPPS) method. Results: Under the 1064 nm laser irradiation, the nanocarrier can accumulate heat quickly for efficient PTT, and then release activated photosensitizer for real-time apoptosis imaging. Thereafter, supplementary PDT can be conducted to kill tumor cells survived from the PTT, and meanwhile the normal tissue can be protected from photo-toxicity. Conclusion: This designed AuHNRs-DTPP nanocarrier with remarkable therapy effect, real-time apoptosis imaging ability and reduced skin damage is of great potential in nanomedicine application. more...

Gold nanoparticles (AuNPs) exhibit great potential for biological applications due to their good biocompatibility and tunable localized surface plasmon resonance (LSPR) properties. Currently, although tuning the aspect ratio of a solid structure or designing a hollow structure has been performed to regulate the LSPR properties of AuNPs, the method of preparing hollow anisotropic AuNPs has rarely been reported. In this study, we designed gold hollow nanorods (AuHNRs) with controllable aspect ratios by a Se-doping Te nanorod-templated method with the assistance of l-cysteine. UV-vis-NIR spectra showed that AuHNRs with an aspect ratio of about 3 could have a LSPR peak in the second near-infrared (NIR-II) window, which is only half of the value required by traditional Au nanorods. Moreover, AuHNRs are nontoxic and capable of loading drugs. In vivo experiment revealed that AuHNRs can be used as contrast agents in multimodal imaging, including photothermal imaging, photoacoustic imaging, and computed tomography imaging, as well as in chemo-photothermal combined therapy of tumor in the NIR-II window. Because light in the NIR-II window has remarkable advantages over that in the first near-infrared (NIR-I) window in biomedical applications, AuHNRs can be used as promising NIR-II-window-responsive multifunctional nanoagents. more...

The miniaturization of gold nanorods exhibits a bright prospect for intravital photoacoustic imaging (PAI) and the hollow structure possesses a better plasmonic property. Herein, miniature hollow gold nanorods (M-AuHNRs) (≈46 nm in length) possessing strong plasmonic absorbance in the second near-infrared (NIR-II) window (1000-1350 nm) are developed, which are considered as the most suitable range for the intravital PAI. The as-prepared M-AuHNRs exhibit 3.5 times stronger photoacoustic signal intensity than the large hollow Au nanorods (≈105 nm in length) at 0.2 optical density under 1064 nm laser irradiation. The in vivo biodistribution measurement shows that the accumulation in tumor of miniature nanorods is twofold as high as that of the large counterpart. After modifying with a tumor-targeting molecule and fluorochrome, in living tumor-bearing mice, the M-AuHNRs group gives a high fluorescence intensity in tumors, which is 3.6-fold that of the large ones with the same functionalization. Moreover, in the intravital PAI of living tumor-bearing mice, the M-AuHNRs generate longer-lasting and stronger photoacoustic signal than the large counterpart in the NIR-II window. Overall, this study presents the fabrication of M-AuHNRs as a promising contrast agent for intravital PAI. more...

Photodynamic therapy (PDT) brings excellent treatment outcome while also causing poor tumor microenvironment and prognosis due to the uncontrolled oxygen consumption. To solve this issue, a novel PDT strategy, oxygenated PDT (maintain the tumor oxygenation before and after PDT) was carried out by a tumor and apoptosis responsive photoactivity conversion nanocomposite (MPPa-DP). Under physiological conditions, this nanocomposite has a low photoactivity. While at H more...

Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) is an important excitatory neurotransmitter receptor that plays a significant role in various neurodegenerative diseases. However, the biological functions of GRIK3 in malignancies are largely unknown because of limited related studies. Here, we primarily reported that the expression of GRIK3 was higher in breast cancer tissues than in adjacent noncancerous tissues. GRIK3 expression was also positively correlated with the prognosis of patients with breast cancer. GRIK3 promoted the proliferation and migration abilities of breast cancer cells and enhanced the growth of orthotopically implanted tumors. Mechanically, GRIK3 influenced a range of signaling pathways and key signal transducers, including two epithelial‐mesenchymal transition regulators, SPDEF and CDH1. Heterogenous expression of SPDEF and CDH1 counteracted the migration and invasion abilities, respectively, of breast cancer cells induced by GRIK3. Moreover, overexpression of GRIK3 increased the expression of mesenchymal markers and decreased the expression of epithelial markers, resulting in the translocation of β‐catenin into the nucleus and the increased β‐catenin transcriptional activity. In conclusion, the present study reported a novel oncogenic role of GRIK3. Meanwhile, GRIK3, as a membrane receptor, may also serve as a potential therapeutic target for the treatment of breast cancer. more...

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery. more...

Ethnopharmacological relevance Cordyceps sinensis has been used as a precious herbal medicine for thousands of years in China. Its polysaccharide fraction has been confirmed possessing immunomodulatory function and we have reported the acid polysaccharide fraction (APSF), from an anamorph of C. sinensis , has stimulating activity on macrophages. The mechanism still needs to be further elucidated. Materials and methods In order to investigate the effects of APSF on macrophage's phenotypes, Ana-1 mouse macrophages were polarized to M2 phenotype by culturing the cells with culture supernatant of H22 cells. M2 phenotype was determined by measuring the expression of TNF-α and checking cell surface markers mannose receptor (MR) and scavenger receptor (SR). After cultured with H22 supernatant for 72 h, the TNF-α level of Ana-1 cells was decreased while the SR and MR expressions were up-regulated, suggesting that Ana-1 cells were polarized towards M2 macrophages. Then the effects of APSF on M2 macrophages were investigated by measuring mRNA levels of TNF-α, inducible nitric oxide synthase (iNOS), IL-12 and IL-10. Nuclear NF-κB was detected by Western blotting. Results APSF treatment increased the expressions of TNF-α, IL-12 and iNOS, and reduced the expression of IL-10 of Ana-1 cells. Besides, the expressions of SR and MR were down-regulated by APSF. And the result of Western blotting showed NF-κB level was decreased in M2 macrophages and up-regulated after APSF treatment. Conclusions APSF may convert M2 macrophages to M1 phenotype by activating NF-κB pathway. more...

Cordyceps sinensis has been regarded as a precious tonic food and herbal medicine in China for thousands of years. The exopolysaccharide (EPS) from an anamorph of Cordyceps sinensis was found to have antitumor immunomodulatory activity. Mature dendritic cells play a role in initiating antitumor immunity, so we try to investigate the effects of EPS on the murine dendritic cell line DCS.Flow cytometry was used to assay the expression levels of cell surface molecules including major histocompatibility complex (MHC)-II, CD40, CD80, and CD86 of DCS cells and their ability to take up antigens. The ability of DCS cells to activate the proliferation of CTLL-2 T cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. IL-12 and TNF-α levels were detected using ELISA. Western blotting was performed to estimate the levels of phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), nuclear factor-κB (NF-κB) p65 and p105.EPS increased the expressions of MHC-II, CD40, CD80, and CD86 of DCS cells and up-regulated their ability to take up antigens. EPS also enhanced their ability to activate the proliferation of CTLL-2 T cells. IL-12 and TNF-α secreted from DCS cells were up-regulated after EPS treatment. Furthermore, EPS significantly caused the decline of p-JAK2 and p-STAT3, significantly increased levels of NF-κB p65 in the nucleus and decreased levels of NF-κB p105 in the cytoplasm.EPS may induce DCS cells to exhibit mature characteristics, and the mechanism involved is probably related to the inhibition of the JAK2/STAT3 signal pathway and promotion of the NF-κB signal pathway. more...

As a freshwater pearl mussel, Hyriopsis cumingii is widely cultured in China to produce pearls. This study was made to explore the antitumor activity of water-soluble polysaccharide (WSP) from mantles of H. cumingii. Cell viability of human hepatocarcinoma HepG2 cells was estimated by MTT method. Cell cycle analysis was determined by flow cytometry. Apoptosis was observed under fluorescence microscopy and confirmed by DNA fragment assay. Reverse transcriptase-polymerized chain reaction (RT-PCR) and immunocytochemistry were carried to evaluate c-myc, bcl-2 and cyclinD1 gene expressions in HepG2 cells. Furthermore, intracellular reactive oxygen species (ROS) production was assessed by flow cytometry. After WSP treatment, the growth of HepG2 cells was inhibited and most of cells arrested in G0/G1 phage (p < .01); apoptotic changes in nucleus and cytoplasm were also observed in WSP-treated cells; percentage of apoptotic rate significantly increased in a dose-dependent manner (p < 0.001); DNA fragmentation was detected in treated HepG2 cells; The mRNA level and protein level of c-myc, bcl-2 and cyclinD1 were decreased in the treated HepG2 cells. ROS was significantly increased in a dose- and time-dependent manner as well. The results suggested that WSP has potent antitumor activity. more...

Two new triterpenoids, 3β-hydroxyoleana-11,13(18)-diene-28,30-dioic acid (1) and 3-oxooleana-11,13(18)-diene-28,30-dioic acid (2), one novel triterpenoid glycoside, 3β-O-(6'-O-methyl-β-D-glucuronopyranosyl)oleana-11,13(18)-dien-28-oic acid (3) along with six known compounds (4 - 9) were isolated from the stem bark of Aralia armata (Wall.) Seem. Their structures were elucidated through extensive spectroscopic methods. The herbicidal activities of these compounds against Bidens pilosa L., an invasive weed in P. R. China, were evaluated. Compounds 3, 5, and 6 exhibited more significant herbicidal activities on B. pilosa than the positive-control pendimethalin. Their possible use as herbicidal chemicals or model compounds deserved more attention. The effects of compounds 1 - 9 on Spodoptera litura cultured cell line Sl-1 cell proliferation and its morphology were also evaluated. The results indicated that compounds 1 - 5 affected Sl-1 cell proliferation. Compound 3 showed more obvious proliferation inhibition activities on Sl-1 cell than the positive-control rotenone. With regard to the effect on morphology, compound 2 significantly changed Sl-1 cell, resulting in cell blebbing and vacuole forming. Triterpenoids aremedicinally and agriculturally important, and cytotoxicity of the three new compounds 1 - 3 deserved further studies. more...

The effects of the immunomodulation and antitumor metastasis of the Chinese medicinal fungus water extract (FWE) were investigated. After B16 melanoma cells were implanted in C57BL/6 mice through their tail veins, the mice were orally administered by FWE at low dose (160 mg/kg/day) and high dose (400 mg/kg/day) for 14 days. The tumor metastatic foci on the lung surface were observed under dissecting microscope. Phagocytosis of peritoneal macrophages was detected through ingesting chicken red blood cells (CRBC) test. Lymphocyte proliferation and the natural killer (NK) cell activity were determined by MTT method and lactate-dehydrogenase (LDH)-release assay, respectively. The expressions of bcl-2 and p53 of livers and lungs were assayed by immunohistochemical method. The results showed that FWE could increase body weights of mice dose dependently. The lung metastasis inhibition rates (MIR) of B16 melanoma cells by low dose and high dose of FWE were 15.5% and 72.7%, respectively. FWE at the two doses enhanced significantly (p more...

There is increasing evidence that psychological stress and depression trigger changes in various biochemical parameters in animals and in human subjects. In order to study these effects, the impact of chronic mild stress (CMS) on rats, and of the subsequent administration of Banxia-houpu decoction and fluoxetine, were studied regarding their effects on the following biochemical parameters: 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in various brain regions, natural killer (NK) cell and lymphokine-activated killer (LAK) cell activities in spleen, serum lipid profiles including total cholesterol (TC), high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc) and triglyceride (TG), liver superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities, serum malondialdehyde (MDA), and interleukin-2 (IL-2) levels. The effects of drug administration on preference behavior for consumption of sucrose solution were also assessed. Rats subjected to CMS exhibited a reduction in sucrose intake, 5-HT, 5-HIAA, IL-2, TC, HDLc and LDLc levels, as well as, diminished NK cell and LAK cell activities. Conversely, liver SOD and NOS activities and serum TG and MDA levels were increased following CMS exposures. Administration of Banxia-houpu decoction and fluoxetine produced beneficial effects on the stressed rats by improving sucrose consumption. This behavioral change was accompanied by amelioration of numbers CMS-induced biochemical changes. Banxia-houpu decoction is a traditional Chinese prescription containing pinellia tuber, magnolia bark, hoelen, perilla herb and ginger rhizome, and has been used for centuries in China to treat mental diseases including depression and schizophrenia. However, the pharmacological profile of the decoction is different from that of fluoxetine. These findings suggest that the therapeutic actions of Banxia-houpu decoction are due to a combination of multiple biochemical effects, and may help to elucidate the mechanisms through which distinct biochemical parameters play a role in the etiology of depression. more...

Both excess dosages of drug and unwanted drug carrier can lead to severe side effects as well as the failure of tumor therapy. Here, an Fe3+–gallic acid based drug delivery system is designed for efficient monitoring of drug release in tumor. Fe3+ and polyphenol gallic acid can form polygonal nanoscale coordination polymer in aqueous solution, which exhibits certain antitumor effect. Importantly, this coordination polymer possesses extremely high doxorubicin (DOX) loading efficacy (up to 48.3%). In vitro studies demonstrate that the fluorescence of DOX can be quenched efficiently when DOX is loaded on the coordination polymer. The acidity in lysosome also triggers the release of DOX and fluorescence recovery simultaneously, which realizes real-time monitoring of drug release in tumor cells. In vivo studies further indicate that this polyphenol-rich drug delivery system can significantly inhibit tumor growth with negligible heart toxicity of DOX. This system with minimal side effects should be a promising nanoplatform for tumor treatment. more...

Cigarette smoke exposure is associated with increased risk of different disorders. Immunological dysfunction especially in macrophages is one of important reasons in the initiation, progression and exacerbation of smoke-related pulmonary illnesses. However, it is still obscure how cigarette smoke impacts the vitality and functions of macrophages. In the present study, we examined the effects of cigarette smoke extract (CSE) on mouse Ana-1 macrophages and tried to elucidate the involved mechanism. The results showed CSE induced cell apoptosis accompanied by increased releasing of lactate dehydrogenase (LDH), mitochondrial injury and oxidative stress. It also inhibited anti-apoptosis protein Bcl-2 expression and promoted pro-apoptosis protein Bax and Bad expressions. Moreover, low-dose CSE increased nuclear NF-κB levels of macrophages; on the contrary, high-dose CSE or long-time treatment decreased it. These observations were in correspondence with changes of intracellular ROS level and antioxidant enzymes’ activity. Furthermore, pretreatment with 10 μM of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) for 1 h significantly enhanced macrophage apoptosis. Taken together, these data implied that mitochondrial dysfunction and oxidative stress played important roles in the injury of Ana-1 cells caused by CSE, which was related to NF-κB pathway; an anti-apoptotic program played a dominant role at low doses/short-term exposure to CSE, whereas a pro-apoptotic program was initiated at high doses/long-term exposure. more...

Sesaminol is one component of sesame oil and has been widely used as the stabilizer to extend the storage period of food oil in China. In this study, we tried to investigate the antioxidant activity of sesaminol on rat pheochromocytoma (PC12) cells oxidative damaged by H2 O2 . Cell viability, LDH level and apoptosis of the PC12 cells were assayed after treatment with sesaminol for 3 h and exposure to H2 O2 . Furthermore, superoxide (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and intracellular ROS were assayed after exposure of the PC12 cells to H2 O2 . The results showed that pre-treatment with sesaminol prior to H2 O2 exposure significantly elevated cell survival rate and SOD, CAT and GSH-Px activity. Meanwhile, sesaminol declined the secreted LDH level, apoptosis rate and ROS level of H2 O2 exposed cells. Thus, sesaminol may protect PC12 against oxidative injury. more...

Dendritic cells (DCs) play an important role in initiating antitumour immune response. Tumour progression usually induces defects in DC maturation and thus tumour-bearing hosts exhibit immunosuppression and tumour escape. The previous studies showed that an exopolysaccharide (EPS) from a fungus, one anamorph of Cordyceps sinensis, inhibited tumour growth via activating immune response in the hosts. In view of the crucial actions of DCs in antitumour immunity, the present study aims to explore the effects of EPS on murine DCs. Murine DCs were derived from the bone marrow of C57BL/6 mice, and the effects of EPS on phenotype molecules and ingestion function of DCs were assayed using flow cytometry. Cytokine expressions of DCs were assayed by reverse transcriptase-PCR. Additionally, the level of phosphorylated signal transducers and activators of transcription 3 (p-STAT3) of DCs was evaluated using Western blotting. The results showed that EPS promoted the levels of surface molecules MHC II, CD40, CD80 and CD86 of DCs and decreased their ingestion ability. The mRNA expressions of cytokines (IL-12p40 and TNF-α) and inducible nitric oxide synthase were up-regulated by EPS. We also found that EPS significantly down-regulated p-STAT3 level of DCs. The results suggested that the promotion of DC's maturation and activation by EPS is probably related to the inhibition of STAT3 phosphorylation. more...

Cordyceps sinensis as a well-known traditional Chinese tonic has many therapeutic functions. In the present study, an acid polysaccharide (APS) was isolated from cultivated Cordyceps mycelia by ion-exchange and sizing chromatography. The protective capacity of APS against H(2)O(2)-induced oxidative damage in rat pheochromocytoma PC12 cells was investigated by measuring cell viability, lactate dehydrogenase (LDH) release, antioxidant enzyme activity, malondialdehyde (MDA) levels and intracellular accumulation of reactive oxygen species (ROS) and Ca(2+). The results demonstrated that pretreatment of PC12 cells with APS, prior to H(2)O(2) exposure, significantly increased the survival of cells and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), and reduced the levels of LDH and MDA. Intracellular accumulation of reactive oxygen species (ROS) and Ca(2+) were also inhibited by APS treatment. In conclusion, APS was found to increase the cellular antioxidant defence capacity, thereby protecting PC12 cells against oxidative stress. more...

The exopolysaccharide (EPS) is a polysaccharide from cultivated Cordyceps sinensis, which possesses immunomodulatory and antitumor effects, was purified by DEAE-32 cellulose and Sephadex G-200 gel. The preliminary characters of EPS were analyzed by IR and GC, and the molecular weight was estimated by gel filtration. The effect of EPS on proliferation ability of lymphocytes from ICR mice was assayed by MTT method. The mRNA and protein expression levels of several cytokines in spleen and thymus cells were detected by RT-PCR and ELISA. The results showed that EPS consists of mannose, glucose, and galactose in a ratio of 23:1:2.6. Its molecular weight is about 1.04 × 10(5). EPS elevated proliferation ability of spleen lymphocytes only at 100 μg/ml after 48 h treatment. Tumor necrosis factor alpha (TNF-α), interferon-α (IFN-γ), and interleukin-2 (IL-2) mRNA levels in splenocytes and thymocytes were increased after EPS treatment for 2, 4, 8, or 20 h. EPS also significantly elevated splenic TNF-α and IFN-γ protein expressions at 100 μg/ml and increased thymic TNF-α and IFN-γ protein levels at 50 and 100 μg/ml. These data indicated that EPS may stimulate cytokine expressions of immunocytes. more...

The acid polysaccharide fraction (APSF) extracted from the mycelia of cultivated Cordyceps sinensis is water-soluble polysaccharide. In this study we evaluated the modulating effects of APSF on murine macrophage cell line RAW264.7. Phagocytotic assay by neutral red and FITC-dextran internalization showed that APSF stimulated the phagocytosis of macrophages. The nitrite levels in the culture supernatant determined using Griess reagent revealed the elevation of NO production after treatment with APSF. RT-PCR and immunocytochemistry assay indicated that APSF promoted both the mRNA and protein expressions of inducible nitric oxide synthase (iNOS). Furthermore, Western blotting demonstrated that NF-kappaB levels in nucleuses increased after APSF treatment, suggesting that APSF probably stimulated macrophage activities by activating the IkappaB-NF-kappaB pathway. more...

In order to explore the effects of exopolysaccharide fraction (EPSF) from one of the anamorph strains of Cordyceps sinensis on immunocyte activity of H22 tumor bearing mice, ICR mice were treated with EPSF for 7 days by intraperitoneal injection at doses of 15 mg/kg (low-dose), 30 mg/kg (mid-dose) and 60 mg/kg (high-dose) after H22 tumor cells were implanted. At the end of the experiments, the tumor weight of each mouse was measured. Phagocytosis of mouse peritoneal macrophages was tested by neutral red uptake. The TNF-alpha expression of macrophages was assayed by ELISA. Proliferation ability and cytotoxicity of spleen lymphocytes were determined by MTT methods. The mRNA levels of cytokine TNF-alpha and IFN-gamma mRNA of spleen lymphocytes were detected by RT-PCR. The results indicated that EPSF not only significantly inhibited the H22 tumor growth, but also significantly elevated immunocytes' activity. It significantly enhanced the phagocytosis capacity of peritoneal macrophages and proliferation ability of spleen lymphocytes at all the three doses; it significantly promoted macrophages' TNF-alpha expression and spleen lymphocytes' cytotoxicity. EPSF also significantly elevated TNF-alpha and IFN-gamma mRNA expression of splenic lymphocytes. This experimental finding suggests that EPSF could elevate the immunocytes' activity in H22 tumor bearing mice. more...

Cordyceps sinensis, one of the most precious traditional Chinese medicines, possesses the antitumor activity, antioxidant activity and the capability of modulating the immune system. In the present study, a fungus strain G1 isolated from wild C. sinensis was identified and initially characterized. A phylogenetic tree was generated based on the sequences of the internal transcribed spacer (ITS) region of related fungi. The analysis of ITS sequence showed that fungus G1 was clustered together with C. sinensis, Tolypocladium cylindrosporum and Tolypocladium inflatum in the phylogenetic tree. Both the morphological character and the ITS sequence analysis establish that fungus G1 is one of the anamorph strains of C. sinensis and belongs to Tolypocladium genus. Furthermore, the polysaccharide (PS) extracted from fungus G1 and its antioxidant activity on H22-bearing mice was investigated. H22 cells were hypodermically injected into the right oxter of each mouse after the ICR mice were treated with PS by means of gavage for 7 days. Then the same administration process continued for 9 days. At the end of the experiments, the tumor weight of each mouse was measured. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in mouse liver, brain and serum, as well as glutathione peroxidase (GSH-Px) activity in mouse liver and brain were assayed. The results showed that the H22 tumor growth was significantly inhibited by PS. Moreover, PS significantly enhanced SOD activity of liver, brain and serum as well as GSH-Px activity of liver and brain in tumor-bearing mice. PS also significantly reduced the level of MDA in liver and brain of tumor-bearing mice. more...

To elucidate the effects of exopolysaccharide from Tolypocladium sinense on murine immunocytes in vitro.Extracted exopolysccharide (EPS) from cultured Tolypocladium sinense. The effects of EPS on mouse immune parameters were detected in vitro using cell culture techniques.The results indicated that EPS might significantly not only promote mouse macrophage neutral red uptake ability and cytotoxicity (P0.05), but also stimulate their thymus lymphocytes proliferation (P0.05).EPS may elevate murine cellular immunity to a certain. more...

The aqueous extract of Cordyceps sinensis (Cs), one of the traditional Chinese medicines, has been used for the treatment of a wide range of disorders for centuries. It is generally accepted that its cultivated Cs fungi possess the same functions as Cs natural herbs. Although polysaccharide from Cs is one of its bioactive compositions, its antitumor ability has not been confirmed. In the present study, we investigated the effects of the exopolysaccharide fraction (EPSF) of a cultivated Cs fungus on c-Myc, c-Fos, and vascular endothelial growth factor (VEGF) expression of tumor-bearing mice. The mice (C57BL/6) were administered three different doses of EPSF peritoneally every 2 days, starting from the day of implantation of B16 melanoma cells through their tail veins for 27 days (14 times). Sections from mouse paraffin-embedded liver and lung tissues were subjected to immunohistochemical analyses. The results of c-Myc, c-Fos, and VEGF expression were analyzed using SimplePCI image analysis software. The c-Myc, c-Fos, and VEGF levels in the lungs and livers of EPSF-treated mice were found to be significantly lower than those of untreated mice (p more...

Banxia-houpu decoction is a safe and effective traditional Chinese medicinal formula used in the treatment of mild and manic-depressive disorders for centuries. There has been increasing interest in its therapeutic application in depression. However, the mechanisms behind behavioural changes are still poorly understood. Chronic mild stress (CMS)-induced preference behaviour change has been used as a model to predict the clinical efficacy of many types of antidepressant treatment. Both EtOH and water extracts (AE and WE) of Banxia-houpu decoction exhibited a significantly increased sucrose intake in the CMS model in rats, but there was no effect in unstressed animals. In the present study, it was found that the c-fos expression in cerebral cortex, hippocampus and striatum corpora were very high in the CMS model in rats. WE and AE at a dose of 130 mg/kg exhibited a significantly decreased c-fos expression in the cerebral regions in CMS model in rats, respectively. The former was more potent than the latter. However, no significant changes in the c-fos expression were observed in unstressed rats treated with the decoction. Fluoxetine not only significantly reduced c-fos expression in all regions in the CMS model in rats, but only showed a marked decrease in c-fos expression in the hippocampus in unstressed animals. A different molecular mechanism of Banxia-houpu decoction and fluoxetine may be implied. The cerebral cortex, hippocampus and striatum conpora might be important structural substrates in the central nervous system mediating the section of the Banxia-houpu decoction on preference behaviour in CMS-induced rats, and fos protein might be the common substrate of the signal transduction process of the decoction. more...

Cigarette smoking is a major pathogenic factor in lung cancer. Macrophages play an important role in host defense and adaptive immunity. These cells display diverse phenotypes for performing different functions. M2 type macrophages usually exhibit immunosuppressive and tumor-promoting characteristics. Although macrophage polarization toward the M2 phenotype has been observed in the lungs of cigarette smokers, the molecular basis of the process remains unclear. In this study, we evaluated the possible mechanisms for the polarization of mouse macrophages that are induced by cigarette smoking (CS) or cigarette smoke extract (CSE). The results showed that exposure to CSE suppressed the production of reactive oxygen species (ROS) and nitric oxide (NO) and down-regulated the phagocytic ability of Ana-1 cells. The CD163 expressions on the surface of macrophages from different sources were significantly increased in in vivo and in vitro studies. The M1 macrophage cytokines TNF-α, IL-12p40 and enzyme iNOS decreased in the culture supernatant, and their mRNA levels decreased depending on the time and concentration of CSE. In contrast, the M2 phenotype macrophage cytokines IL-10, IL-6, TGF-β1 and TGF-β2 were up-regulated. Moreover, phosphorylation of JAK2 and STAT3 was observed after the Ana-1 cells were treated with CSE. In addition, pretreating the Ana-1 cells with the STAT3 phosphorylation inhibitor WP1066 inhibited the CSE-induced CD163 expression, increased the mRNA level of IL-10 and significantly decreased the mRNA level of IL-12. In conclusion, we demonstrated that the M2 polarization of macrophages induced by CS could be mediated through JAK2/STAT3 pathway activation. more...

Cordyceps sinensis (Chinese caterpillar fungus) is a fungus parasitic on the larvae of Lepidoptera and has been considered to be a precious tonic food and herbal medicine since ancient times in China. Recently, some fungal strains have been isolated from the fruiting bodies of wild C. sinensis, and some of them have been reported to show the same properties as the natural product. In the present study, an EPSF (exopolysaccharide fraction) was prepared from cultivated C. sinensis and its effects on B16 melanoma-bearing mice were investigated. Three doses of EPSF were intraperitoneally administered every 2 days after the day of tumour-cell injection. The experiment was terminated on day 28. Phagocytosis of peritoneal macrophages and proliferation of spleen and thymus lymphocytes were assayed. The tumour metastatic foci on the lung and liver surface were checked. The expression of oncoprotein Bcl-2 in livers and lungs was assayed by a immunohistochemical method. The results showed that EPSF significantly enhanced the Neutral Red uptake capacity of peritoneal macrophages (60 mg/kg, P more...