A homologous-targeting cGAS-STING agonist multimodally activates dendritic cells for enhanced cancer immunotherapy.

Herein, we developed a doxorubicin (Dox)-loaded and 4T1 cancer cell membrane-modified hydrogenated manganese oxide nanoparticles (mHMnO-Dox) to elicit systemic antitumor immune responses. The results revealed that mHMnO-Dox actively recognized tumor cells and then effectively delivered Dox into the cells. Upon entering tumor cells, the mHMnO-Dox underwent rapid degradation and abundant release of Mn2+ and chemotherapeutic drugs. The released Mn2+ not only catalysed a Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also activated the cGAS-STING pathway to boost dendritic cell (DC) maturation. This process increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. In addition, the released Dox could contribute to a chemotherapeutic effect, while activating DC cells and subsequently intensifying immune responses through immunogenic cell death (ICD) of tumor cells. Consequently, the mHMnO-Dox suppressed the primary and distal tumor growth and inhibited tumor relapse and metastasis, as well as prolonged the lifespan of tumor-bearing mice. Thus, the mHMnO-Dox multimodally activated DC cells to demonstrate synergistic antitumor activity, which was mediated via the activation of the cGAS-STING signalling pathway to regulate tumor microenvironment, ICD-mediated immunotherapy and ROS-mediated CDT. These findings suggest the therapeutic potential of mHMnO-Dox in cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A cancer cell membrane-camouflaged hydrogenated mesoporous manganese oxide (mHMnO) has been developed as a cGAS-STING agonist and ICD inducer. The mHMnO effectively induced abundance of ROS production in cancer cells, which caused cancer cell death and then promoted DC maturation via tumour-associated antigen presentation. Meanwhile, the mHMnO significantly activated cGAS-STING pathway to facilitate DC maturation and cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment, which further enhanced tumour immune response. In addition, the combination of the mHMnO and Dox could synergistically promote tumour ICD and then multimodally induce DC maturation, achieving an enhanced CIT. Overall, this study provides a potential strategy to design novel immunologic adjuvant for enhanced CIT.

NIR-IIb fluorescence antiangiogenesis copper nano-reaper for enhanced synergistic cancer therapy.

The formation of blood vessel system under a relatively higher Cu2+ ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.

ICSDA: a multi-modal deep learning model to predict breast cancer recurrence and metastasis risk by integrating pathological, clinical and gene expression data.

Breast cancer patients often have recurrence and metastasis after surgery. Predicting the risk of recurrence and metastasis for a breast cancer patient is essential for the development of precision treatment. In this study, we proposed a novel multi-modal deep learning prediction model by integrating hematoxylin & eosin (H&E)-stained histopathological images, clinical information and gene expression data. Specifically, we segmented tumor regions in H&E into image blocks (256 × 256 pixels) and encoded each image block into a 1D feature vector using a deep neural network. Then, the attention module scored each area of the H&E-stained images and combined image features with clinical and gene expression data to predict the risk of recurrence and metastasis for each patient. To test the model, we downloaded all 196 breast cancer samples from the Cancer Genome Atlas with clinical, gene expression and H&E information simultaneously available. The samples were then divided into the training and testing sets with a ratio of 7: 3, in which the distributions of the samples were kept between the two datasets by hierarchical sampling. The multi-modal model achieved an area-under-the-curve value of 0.75 on the testing set better than those based solely on H&E image, sequencing data and clinical data, respectively. This study might have clinical significance in identifying high-risk breast cancer patients, who may benefit from postoperative adjuvant treatment.

[Granulation of Yangxue Qingnao Granules in fluidized bed based on near-infrared spectroscopy].

To realize the real-time monitoring of the production process of Yangxue Qingnao Granules and improve the inter-batch consistency of granule quality in the granulation process, this study established a near-infrared quantitative prediction model of moisture, particle size, bulk density, and angle of repose in the fluidized bed granulation process of Yangxue Qingnao Granules based on near-infrared spectroscopy(NIRS). The near-infrared spectra were collected from 355 samples in 12 batches in the granulation process by integrating the sphere detection module of the near-infrared spectrometer. In combination with the pretreatment methods such as the first derivative, multiplicative scatter correction(MSC), and standard normal variate(SNV), the model was established by partial least squares(PLS) regression. The root mean square error of prediction(RMSEP) of moisture was 0.347 and R_P~2 was 0.935. The RMSEP of the D_(50) particle size model was 38.4 and R_P~2 was 0.980. The RMSEPs of bulk density and angle of repose were 0.018 8 and 0.879, with R_P~2 of 0.085 9 and 0.958. The results showed that the prediction of the PLS quantitative model combined with NIRS was accurate, and this model can be applied to the monitoring of key quality attributes in the fluidized bed granulation of Chinese medicinal granules in the production scale.

Amorphous ferric oxide-coating selenium core-shell nanoparticles: a self-preservation Pt(IV) platform for multi-modal cancer therapies through hydrogen peroxide depletion-mediated anti-angiogenesis, apoptosis and ferroptosis.

A self-preservation Pt(IV) nanoplatform, amorphous ferric oxide-coating selenium core-shell nanoparticles (iAIO@NSe-Pt), was developed for H2O2 depletion-mediated tumor anti-angiogenesis, apoptosis, and ferroptosis. Upon entry into the blood, the ferric oxide shell effectively blocked the contact Pt(IV) prodrug with reduced molecules, then avoided the inactivation of the Pt(IV) prodrug and increased its accumulation in the tumor. After entering cancer cells, iAIO@NSe-Pt caused a series of cascade reactions: (1) AIO on the surface of iAIO@NSe-Pt quickly dissolved, released an abundance of Fe(II) because of the weakly acidic tumor microenvironment, and then catalyzed cellular H2O2 into highly toxic ˙OH, resulting in cellular H2O2 deficiency and cell ferroptosis. (2) The platinum(IV) prodrugs were exposed and quickly reduced to highly toxic Pt(II) by depleting GSH. This process inactivated GPX4, promoted ROS accumulation, and further accelerated ferroptosis. In addition, the generated Pt(II) quickly inhibited DNA replication, achieving effective apoptotic cell death. Meanwhile, Pt(II) inactivated SOD1, which blocked the synthesis of cellular H2O2 and accelerated ROS (superoxide anion radical) accumulation. (3) The deficiency of cellular H2O2 significantly inhibited the expression of vascular endothelial growth factor-A (VEGF-A), blocking tumor angiogenesis and then improving the anticancer effect. (4) After such a cascade reaction, the exposed NSe successively disrupted mitochondrial respiration and inhibited cancer angiogenesis, further inducing cancer cell death. Collectively, our functional and mechanical investigation suggested that iAIO@NSe-Pt exhibits excellent tumor targeting, biocompatibility and anti-tumor efficiency in vitro and in vivo, and provides a novel example of a self-preservation Pt(IV) nanoplatform for H2O2 depletion-mediated tumor anti-angiogenesis, apoptosis, and ferroptosis, showing great promise for future clinical use.

A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery.

The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures.

The outbreak of a novel febrile respiratory disease called COVID-19, caused by a newfound coronavirus SARS-CoV-2, has brought a worldwide attention. Prioritizing approved drugs is critical for quick clinical trials against COVID-19. In this study, we first manually curated three Virus-Drug Association (VDA) datasets. By incorporating VDAs with the similarity between drugs and that between viruses, we constructed a heterogeneous Virus-Drug network. A novel Random Walk with Restart method (VDA-RWR) was then developed to identify possible VDAs related to SARS-CoV-2. We compared VDA-RWR with three state-of-the-art association prediction models based on fivefold cross-validations (CVs) on viruses, drugs and virus-drug associations on three datasets. VDA-RWR obtained the best AUCs for the three fivefold CVs, significantly outperforming other methods. We found two small molecules coming together on the three datasets, that is, remdesivir and ribavirin. These two chemical agents have higher molecular binding energies of - 7.0 kcal/mol and - 6.59 kcal/mol with the domain bound structure of the human receptor angiotensin converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein, respectively. Interestingly, for the first time, experimental results suggested that navitoclax could be potentially applied to stop SARS-CoV-2 and remains to further validation.

Protective Role of a New Polysaccharide Extracted from Lonicera japonica Thunb in Mice with Ulcerative Colitis Induced by Dextran Sulphate Sodium.

Lonicera japonica Thunb is a traditional Chinese herbal medicine for treating intestinal inflammation. The extraction method of Lonicera japonica Thunb polysaccharide (LJP) has been developed previously by our research group. In this study, a Fourier transform infrared spectrometer (FT-IR) was used to perform a qualitative analysis of LJP and a precolumn derivatization high-performance liquid chromatography (HPLC) ((Palo Alto, CA, USA) method was used to explore the monosaccharide composition of LJP. Then, we studied the effect of LJP on the intestinal flora and immune functions of dextran sulfate sodium- (DSS-) induced colitis ulcerative mouse models. The results showed that LJP was consisted of 6 types of monosaccharides and had the characteristic absorption of typical polysaccharides. LJP can increase significantly the weight, organ index, serum cytokines (interleukin, tumor necrosis factor, and interferon-γ), secretory immunoglobulin A (SIgA) concentration, and natural killer (NK) cell and cytotoxic lymphocyte (CTL) activities in DSS-treated mice. The results of intestinal flora showed that a high dose (150 mg kg-1) of LJP had the best effects on improving the intestinal probiotics (Bifidobacterium and Lactobacilli) and antagonizing the pathogenic bacteria (Escherichia coli and Enterococcus). In addition, the measurement results of the spleen lymphocyte apoptosis confirmed from another perspective that LJP had protective effects of immune cells for DSS-treated mice.

Probing antiviral drugs against SARS-CoV-2 through virus-drug association prediction based on the KATZ method.

It is urgent to find an effective antiviral drug against SARS-CoV-2. In this study, 96 virus-drug associations (VDAs) from 12 viruses including SARS-CoV-2 and similar viruses and 78 small molecules are selected. Complete genomic sequence similarity of viruses and chemical structure similarity of drugs are then computed. A KATZ-based VDA prediction method (VDA-KATZ) is developed to infer possible drugs associated with SARS-CoV-2. VDA-KATZ obtained the best AUCs of 0.8803 when the walking length is 2. The predicted top 3 antiviral drugs against SARS-CoV-2 are remdesivir, oseltamivir, and zanamivir. Molecular docking is conducted between the predicted top 10 drugs and the virus spike protein/human ACE2. The results showed that the above 3 chemical agents have higher molecular binding energies with ACE2. For the first time, we found that zidovudine may be effective clues of treatment of COVID-19. We hope that our predicted drugs could help to prevent the spreading of COVID.

Protective Effect of a Novel Polysaccharide from Lonicera japonica on Cardiomyocytes of Mice Injured by Hydrogen Peroxide.

Lonicera japonica is a traditional Chinese herbal medicine with antioxidation, anti-inflammatory, antibacterial, and immunoregulation functions. A method to isolate polysaccharides from Lonicera japonica (LJP) has been reported previously by our group. We also reported previously that LJP was consisted of 6 types of monosaccharides and had the characteristic absorption of typical polysaccharides. In this study, we investigated the protective effect of LJP on cardiomyocytes of mice injured by hydrogen peroxide (H2O2). The results showed that LJP can increase the cardiomyocyte viability and the activities of the enzyme (SOD, CAT, GSH-Px, AST, CPK, and LDH) in cardiomyocytes of mice injured by hydrogen peroxide. The results of intracellular ROS contents showed that a high dose (40 µg mL-1) of LJP had the best effects on protecting the cardiomyocytes of mice injured by H2O2. In addition, the measurement results of the cardiomyocyte apoptosis and the activity of caspase-3, caspase-8, and caspase-9 in cardiomyocytes confirmed this conclusion from another perspective.

Oxygen Vacancy Defect-Induced Activity Enhancement of Gd Doping Magnetic Nanocluster for Oxygen Supplying Cancer Theranostics.

This work finds that Fe3O4 nanoclusters can rearrange by Gd doping and then self-assemble to a hollow magnetic nanocluster (HMNC), providing larger magnetic moments to obtain an excellent MRI capability and increasing the number of oxygen vacancies in HMNC. The hollow structure makes platinum(IV) prodrugs effectively load into HMNC. Second, plenty of oxygen vacancy defects can capture oxygen molecules, enhance the catalytic activity of HMNC, and then promote intracellular ROS generation. On the basis of this, a targeting iRGD-labeled HMNC nanosystem (iHMNCPt-O2) is developed through loading oxygen molecules and platinum(IV) prodrugs for chemo- and chemodynamic therapy of cancer. This nanosystem shows an excellent response ability to weak acid and GSH, which can cause a series of cascade reactions in a cell. These cascade reactions are dramatically enhanced at the intracellular ROS level, cause mitochondria and DNA damage, and then induce cancer cell death. Besides, systemic delivery of iHMNCPt-O2 significantly enhanced the MRI contrast signal of tumors and improved the quality of MR images, accurately diagnosing tumors. Therefore, this work provides a novel method for accelerating the Fenton-like reaction and enhancing the MRI capability and fabricates a promising "all-in-one" system to overwhelm the problems of cancer theranostic.

A pH-responsive platform combining chemodynamic therapy with limotherapy for simultaneous bioimaging and synergistic cancer therapy.

Chemodynamic therapy (CDT) was widely exploited for cancer therapy and expected to replace traditional anticancer drug therapies. Generally, CDT needs to combine with extra therapeutic methods for obtaining the optimal therapeutic efficacy of cancer. Herein, a multifunctional theranostic platform combing CDT with limotherapy was developed via nanoselenium (nano-Se)-coated manganese carbonate-deposited iron oxide nanoparticle (MCDION-Se). MCDION-Se could release abundant of Mn2+ ions that catalyzed H2O2 into hydroxyl radicals (·OH) via a Fenton-like reaction, effectively inducing the apoptosis of cancer cells. Besides, nano-Se coated onto MCDION-Se also dramatically activated superoxide dismutase (SOD) and promoted the generation of superoxide anion radicals (SOARs) in tumor tissue. Subsequently, a high content of H2O2 was produced via SOD catalysis of SOARs, further enhancing CDT efficiency. Meanwhile, the nano-Se and Mn2+ ions inhibited the generation of adenosine triphosphate (ATP), thus starving cancer cells. In addition, in vitro and in vivo experiments showed that MCDION-Se could effectively enhance the contrast of tumor tissue and improve the quality of magnetic resonance imaging (MRI). Overall, this work provided a nanoplatform that combined CDT with limotherapy for cancer therapy and simultaneously utilized MRI for monitoring the treatment of tumors.

Curcumin ameliorates gestational diabetes in mice partly through activating AMPK.

CONTEXT: In vitro and in vivo research has shown that curcumin can alleviate diabetes and the relevant complications. OBJECTIVE: To investigate the effect of curcumin on gestational diabetes (GD). MATERIALS AND METHODS: C57 BL/KsJdb/+(db/+) mice and C57 BL/KsJ+/+ mice (10-12 weeks old) were divided into four groups (n = 15): normal pregnancy (C57 BL/KsJ+/+), GD (C57 BL/KsJdb/+), GD plus low dose curcumin (50 mg/kg, orally gavage every day) and GD plus high dose curcumin (100 mg/kg, orally gavage every day). The tolerance of glucose and insulin were measured on gestation day 10. Body weight at birth and litter size of offspring were investigated, and the expression of oxidative stress factors [thiobarbituric acid reactive substance (TBARS), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)] and AMP-activated protein kinase (AMPK), phospho-AMPK, histone deacetylases 4 (HDAC4), pHDAC4 and glucose-6-phosphatase (G6Pase) in the livers were analyzed by ELISA and Western blot on gestation day 20. RESULTS: High dose curcumin could partly ameliorate the intolerance of glucose and insulin, and completely restore the litter size and the body weight of GD mice through decreased TBARS expression (p < 0.05) and increased GSH, SOD and CAT expression (p < 0.05). Enhanced AMPK activation, accompanied with decreased HDAC4 and G6Pase expression (p < 0.05) were partly contributed to the alleviation of GD mediated by curcumin. CONCLUSIONS: Although further detailed mechanism needs to be deciphered, curcumin can be considered as an alternative treatment for gestational diabetes.

The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials.

BACKGROUNDS AND OBJECTIVE: Several clinical trials have shown that grape seed extract can reduce blood pressure, but the results are often irreproducible. We therefore sought to systematically evaluate the impact of grape seed extract treatment on the changes of systolic/diastolic blood pressure (SBP/DBP) by meta-analyzing available randomized controlled trials. METHODS: Trial selection and data extraction were completed independently by 2 investigators. Effect-size estimates were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). RESULTS: Twelve articles involving 16 clinical trials and 810 study subjects were analyzed. Overall analyses found significant reductions for SBP (WMD = -6.077; 95% CI: -10.736 to -1.419; P = 0.011) and DBP (WMD = -2.803; 95% CI: -4.417 to -1.189; P = 0.001) after grape seed extract treatment. In subgroup analyses, there were significant reductions in younger subjects (mean age < 50 years) for SBP (WMD = -6.049; 95% CI: -10.223 to -1.875; P = 0.005) and DBP (WMD = -3.116; 95% CI: -4.773 to -1.459; P < 0.001), in obese subjects (mean body mass index ≥ 25 kg/m) for SBP (WMD = -4.469; 95% CI: -6.628 to -2.310; P < 0.001), and in patients with metabolic syndrome for SBP (WMD = -8.487; 95% CI: -11.869 to -5.106; P < 0.001). Further meta-regression analyses showed that age, body mass index, and baseline blood pressure were negatively associated with the significant reductions of SBP and DBP after treatment. There was no indication of publication bias. CONCLUSION: Our findings demonstrate that grape seed extract exerted a beneficial impact on blood pressure, and this impact was more obvious in younger or obese subjects, as well as in patients with metabolic disorders. In view of the small sample size involved, we agree that confirmation of our findings in a large-scale, long-term, multiple-dose randomized controlled trial, especially among hypertensive patients is warranted.

Ubiquinol-10 supplementation activates mitochondria functions to decelerate senescence in senescence-accelerated mice.

AIM: The present study was conducted to define the relationship between the anti-aging effect of ubiquinol-10 supplementation and mitochondrial activation in senescence-accelerated mouse prone 1 (SAMP1) mice. RESULTS: Here, we report that dietary supplementation with ubiquinol-10 prevents age-related decreases in the expression of sirtuin gene family members, which results in the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a major factor that controls mitochondrial biogenesis and respiration, as well as superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also increase mitochondrial complex I activity and decrease levels of oxidative stress markers, including protein carbonyls, apurinic/apyrimidinic sites, malondialdehydes, and increase the reduced glutathione/oxidized glutathione ratio. Furthermore, ubiquinol-10 may activate Sirt1 and PGC-1α by increasing cyclic adenosine monophosphate (cAMP) levels that, in turn, activate cAMP response element-binding protein (CREB) and AMP-activated protein kinase (AMPK). INNOVATION AND CONCLUSION: These results show that ubiquinol-10 may enhance mitochondrial activity by increasing levels of SIRT1, PGC-1α, and SIRT3 that slow the rate of age-related hearing loss and protect against the progression of aging and symptoms of age-related diseases.

[Anti-HIV activities of Achyranthes bidentata polysaccharide sulfate in vitro and in vivo].

Achyranthes bidentata polysaccharide sulfate (ABPS) was a sulfated derivate derived from Achyranthes bidentata polysaccharide (ABP) which was isolated and identified from Chinese herb Achyranthes bidentata. The anti human immunodeficiency virus type 1 (HIV-1) activities were studied in vitro and in vivo. ABPS was found to inhibit HIV-1 reverse transcriptase and integrase with the 50% inhibiting concentration (IC60) of (2.948 +/- 0.556) micromol x L(-1) and (0.155 +/- 0.030) micromol x L(-1), respectively, but the parent compound ABP was not effective. ABPS inhibited HIV-1 P24 antigen with IC50 of (0.082 +/- 0.044) micromol x L(-1) and selective index (SI) of > (358 +/- 148) in MT-4 cell cultures acutely infected with HIV-1 IIIB virus, and with IC50 of (11.80 +/- 5.90) micromol x L(-1) and SI of > (24.2 +/- 12.1) in PBMC cell cultures acutely infected with clinical isolated zidovudine resistant HIV-1 virus, but there was no activity even at its concentration of 500 micromol x L(-1) in latent infection of H9/HIV-1 IIIB cell cultures. 5% sera taken from rats after intraperitoneal injection from rats with ABPS 125 mg x kg(-1) once or mice with 3 mg x kg(-1) qd for 20 days effectively inhibited HIV-1 P24 in MT-4 cell cultures, but those had no inhibitory effect when given orally. The results suggested that ABPS is a promising HIV-1 inhibitor, active on HIV-1 reverse transcriptase, integrase in vitro and HIV-1 P24 antigens in cell cultures, it was well absorbed by intraperitoneal injection but poor in oral bioavailability. It warrants further study.

[Effects of LbGp on the intracellular free calcium concentration of cardiomyocytes induced by hypoxia and KCl].

OBJECTIVE: Hypoxia/KCl injury model in the cultured neonatal rat cardiomyocytes (CMs) was established to investigate the protective effect of Lycium barbanun Glycopeptide (LbGp) on calcium overload. METHOD: Cultured neonatal rat CMs were divided into three groups, namely normal control, hypoxia groups and LbGp-treated group. CMs in LbGp-treated group and hypxia group were cultured in an incubator ventilated with 95% N2 and 5% CO2 with or without LbGP. CMs viability under hypoxia was measured by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide colorimetry (MTT). The intracellular free calcium concentration in cardiomyocytes was measured by laser confocal microscope with Fura-3/AM as a calcium indicator. The protective effects of LbGp on the CMs treated by KCl (60 mmol x L(-1)) was observed. RESULT: As compared with normal controls, the degree of MTT metabolism was significantly reduced (P < 0.01) in hypoxic group and slightly reduced in LbGp (P < 0.05). Hypoxia-induced enhancement of intracellular calcium ([Ca2+]i) was attenuated by LbGp significantly (P < 0.01). Moreover, KCl-induced enhancement of [Ca2+]i was also reduced by LbGp at the doses of 25, 50, 100 microg x mL(-1) in a concentration-dependent manner. CONCLUSION: The result suggested that LbGp is able to increase the survival ratio and inhibit the enhancement of the intracellular free calcium concentration in cardiomyocytes induced by hypoxia and high potassium. One of the mechanisms is that LbGp acts on L-type calcium channels.

[Physical-chemical properties and structure elucidation of abPS isolated from the root of Achyranthes bidentata].

AIM: To study the physicochemical properties and the structure of Achyranthes bidentata polysaccharide (AbPS). METHODS: AbPS was isolated from the roots of Achyranthes bidentata Bl., and purified by gel filtration chromatography. The distribution of the molecular weight of AbPS was determined by ESI-MS. The structure of AbPS was deduced by methylation analysis, reductive-cleavage and 13CNMR spectroscopy. RESULTS: AbPS was shown to compose of fructose residues and glucose residues and the molar ratio was 8:1. AbPS contain 2,1-linked fructose residue, 2,1-linked fructose residue, 1,2,6-linked fructose residue, terminal fructose residue and terminal glucose residue. CONCLUSION: AbPS is a fructan and belong to graminan.

[Studies on physico-chemical properties and hypoglycemic activity of complex polysaccharide AMP-B from Atractylodes macrocephala Koidz].

AIM: To isolate a complex polysaccharide (AMP-B) from Atractylodes macrocephala Koidz and study its phtsico-chemical properties and hypoglycemic activity. METHODS: The root of Atractylodes macrocephala K. was extracted with water and precipitated with ethanol, dialyzed against water and freeze-dried to get the crude polysaccharides (AMP). A complex polysaccharide (AMP-B) was isolated and purified on DEAE-cellulose column. The model of diabetes rats was established with alloxan injection through the tail vein. Male rats were divided into 5 groups: the normal group, the control group, and three AMP-B-fed groups. Measuring the blood glucose, water and food consumption, thymus and pancreas index, and studying cut sections of pancreas tissues. RESULTS: AMP-B is a complex-polysaccharide, elemental analysis of AMP-B shown C 32.84%, H 5.68%, and N 1.79%. The neutral polysaccharide content of AMP-B was 50.3%, uronic acid was 40.4%, and protein was 11.5%. Monosaccharide composition of AMP-B was determined by GC, AMP-B composed of Glc, Gal, Man, Ara and Rha in a molar ratio of 3.0:2.5:1.3:3.5:1.0. AMP-B was found to reduce blood glucose level in alloxan-diabetic rats markedly at doses of 50, 100 and 200 mg.kg-1 by ig, but no effect in normal rat. AMP-B was found to decrease the consumption of water and food, recover pancreas damage of diabetic rats obviously, inhibited the atrophy of thymus and pancreas of the diabetic rats induced by alloxan. CONCLUSION: AMP-B showed significant hypoglycemic effect on the experimental hyperglycemias rats induced by alloxan.

Structural elucidation and antitumor activity of a fructan from Cyathula officinalis Kuan.

A fructan named CoPS3 was isolated from Cyathula officinalis Kuan. The structure of CoPS3 was determined by methylation, by the reductive-cleavage method combined with GC-MS analysis, and both 1D and 2D 1H and 13C NMR spectroscopy. These results show that CoPS3 is a graminans-type fructan that is comprised of a beta-D-fructofuranosyl backbone having residues linked (2-->1)- and (2-->6) with branches and an alpha-D-glucopyranose residue on the nonreducing end of the fructan chain. Each branch is terminated by a beta-D-Fruf residue. Bioassay showed that it could inhibit growth of Lewis pulmonary carcinoma implanted in mice.