Vertical VOPO4·2H2O Nanosheets with Richly Exposed (200) Plane Enable Fast-Kinetics High-Mass-Loading Cathodes for Zn-Ion Batteries.

Extending the layer spacing of the (001) planes to regulate the mobility of Zn2+ is widely adopted to optimize the performance of VOPO4·2H2O cathode for zinc-ion batteries. However, the unique function originating from other planes is often neglected. Herein, an effective in situ conversion methodology is proposed for the synthesis of the (200) oriented growth of vertical VOPO4·2H2O nanosheets with oxygen vacancies (VOd-VOPO4). Theoretical simulation and ex situ characterizations collaboratively demonstrate that the richly exposed (200) plane with tetragonal channels can offer quick pathways for in-layer and cross-layer migration of Zn2+, exhibiting enhanced transfer kinetics with improved reversible capacity. Meanwhile, efficient electron migration in VOd-VOPO4 is guaranteed by the introduction of oxygen vacancies. Thus, the as-prepared VOd-VOPO4 harvests exceptional discharge capacity, impressive rate capability, and remarkable long-cycle stability at high mass loading. Notably, the VOd-VOPO4 electrode (15 mg cm-2) provides a capacity of 213.5 mAh g-1 with an ultrahigh areal capacity of 3.02 mAh cm-2 at 0.1 A g-1, showing great potential for applications. This study highlights the orientated growth strategy for facilitating ion storage and migration, offering novel perspectives on the development of high-performance electrodes and beyond.

Caffeic acid combined with arabinoxylan or ß-glucan attenuates diet-induced obesity in mice via modulation of gut microbiota and metabolites.

Polyphenols and dietary fibers in whole grains are important bioactive compounds to reduce risks for obesity. However, whether the combination of the two components exhibits a stronger anti-obesity effect remains unclear. Caffeic acid is a major phenolic acid in cereals, and arabinoxylan and ß-glucan are biological macromolecules with numerous health benefits. Here, we investigated the effect of caffeic acid combined with arabinoxylan or ß-glucan on glucose and lipid metabolism, gut microbiota, and metabolites in mice fed a high-fat diet (HFD). Caffeic acid combined with arabinoxylan or ß-glucan significantly reduced the body weight, blood glucose, and serum free fatty acid concentrations. Caffeic acid combined with ß-glucan effectively decreased serum total cholesterol levels and hepatic lipid accumulation, modulated oxidative and inflammatory stress, and improved gut barrier function. Compared with arabinoxylan, ß-glucan, and caffeic acid alone, caffeic acid combined with arabinoxylan or ß-glucan exhibited a better capacity to modulate gut microbiota, including increased microbial diversity, reduced Firmicutes/Bacteroidetes ratio, and increased abundance of beneficial bacteria such as Bifidobacterium. Furthermore, caffeic acid combined with ß-glucan reversed HFD-induced changes in microbiota-derived metabolites involving tryptophan, purine, and bile acid metabolism. Thus, caffeic acid and ß-glucan had a synergistic anti-obesity effect by regulating specific gut microbiota and metabolites.

PELI2 regulates early B-cell progenitor differentiation and related leukemia via the IL-7R expression.

Little is known about the transition mechanisms that govern early lymphoid lineage progenitors from common lymphoid progenitors (CLPs). Pellino2 (PELI2) is a newly discovered E3 ubiquitin ligase, which plays important roles in inflammation and immune system. However, the physiological and molecular roles of PELI2 in the differentiation of immune cells are largely unknown. Here, by using a conditional knockout mouse model, we demonstrated that PELI2 is required for the early B-cell development and stressed hematopoiesis. PELI2 interacted with and stabilized PU.1 via K63- polyubiquitination to regulate IL-7R expression. The defects of B cell development induced by PELI2 deletion were restored by overexpression of PU.1. Similarly, PELI2 promoted TCF3 protein stability via K63- polyubiquitination to regulate IL-7R expression, which is required for the proliferation of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. These results underscore the significance of PELI2 in both normal B lymphopoiesis and malignant B-cell acute lymphoblastic leukemia via the regulation of IL-7R expression, providing a potential therapeutic approach for BCP-ALL.

Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage.

Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by the fusion gene BCR: ABL1. Drug resistance to tyrosine kinase inhibitors (TKIs) due to BCR: ABL1 mutation and residual leukemia stem cells (LSCs) remain major challenges for CML treatment. Here, we revealed the requirement of VDR in the progression of CML, in which VDR was upregulated by BCR: ABL1, accounting for its high expression. Interestingly, VDR knockdown inhibited the CML cell proliferation driven by BCR: ABL1 regardless of its mutations with resistance to TKIs. Mechanistically, VDR transcriptionally regulated DDIT4 expression, and the inhibition of DDIT4 triggered DNA damage-induced senescence via p53 signaling activation in CML cells. Furthermore, VDR deficiency was sufficient to not only ameliorate the disease burden and progression in primary CML mice but also reduce the self-renewal of CML-LSCs. Together, our study demonstrated that targeting VDR is a promising strategy to overcome TKI resistance and eradicate leukemia stem cells in CML.

Effects of Oats, Tartary Buckwheat, and Foxtail Millet Supplementation on Lipid Metabolism, Oxido-Inflammatory Responses, Gut Microbiota, and Colonic SCFA Composition in High-Fat Diet Fed Rats.

Coarse cereals rich in polyphenols, dietary fiber, and other functional components exert multiple health benefits. We investigated the effects of cooked oats, tartary buckwheat, and foxtail millet on lipid profile, oxido-inflammatory responses, gut microbiota, and colonic short-chain fatty acids composition in high-fat diet (HFD) fed rats. Rats were fed with a basal diet, HFD, oats diet (22% oat in HFD), tartary buckwheat diet (22% tartary buckwheat in HFD), and foxtail millet diet (22% foxtail millet in HFD) for 12 weeks. Results demonstrated that oats and tartary buckwheat attenuated oxidative stress and inflammatory responses in serum, and significantly increased the relative abundance of Lactobacillus and Romboutsia in colonic digesta. Spearman's correlation analysis revealed that the changed bacteria were strongly correlated with oxidative stress and inflammation-related parameters. The concentration of the butyrate level was elevated by 2.16-fold after oats supplementation. In addition, oats and tartary buckwheat significantly downregulated the expression of sterol regulatory element-binding protein 2 and peroxisome proliferator-activated receptors γ in liver tissue. In summary, our results suggested that oats and tartary buckwheat could modulate gut microbiota composition, improve lipid metabolism, and decrease oxidative stress and inflammatory responses in HFD fed rats. The present work could provide scientific evidence for developing coarse cereals-based functional food for preventing hyperlipidemia.

Dietary fructose and risk of metabolic syndrome in Chinese residents aged 45 and above: results from the China National Nutrition and Health Survey.

BACKGROUND: A growing number of researches supported that dietary fructose was associated with most of the key features of metabolic syndrome (MetS). However, there was no related epidemiological studies among Chinese population, despite the sharp increase in MetS cases. This study explores the relationship between dietary fructose and MetS among Chinese residents aged 45 and above. METHODS: A total of 25,528 participants (11,574 males and 13,954 females) were included in this nationwide representative cross-sectional study of China National Nutrition and Health Survey. Dietary fructose intake was assessed by 3-day 24-h dietary records. MetS was defined by the International Diabetes Federation and Chinese Diabetes Society criteria. RESULTS: The consumption of dietary fructose was 11.6 g/day for urban residents and 7.6 g/day for rural residents. Fruits and vegetables as well as their products were the main sources of fructose intake. There was no association between dietary fructose intake and the odds of having MetS in both urban (P = 0.315) and rural residents (P = 0.230) after adjustment for confounding factors. Moreover, for urban residents participating physical activities, the odds of having MetS in the fourth quartiles (OR: 0.67; 95%CI: 0.52-0.87) was lower than that in the first quartile. In the sensitivity analysis, a significant reduction in the odds of having MetS was also found in the fourth quartiles (OR, 95%CI: 0.68, 0.51-0.90; 0.67, 0.49-0.91; 0.74, 0.56-0.99) compared with the first quartile when excluding smokers, alcohol users, and underweight/obesity, respectively. And there was no association between dietary fructose intake and the odds of having MetS after multivariate adjustment stratified by gender, smoking and alcohol use. CONCLUSIONS: Under the current dietary fructose intake status, there was no association between dietary fructose intake and the odds of having MetS among Chinese residents aged 45 and above. Physical activity and relatively low fructose intake may have a beneficial synergistic effect on MetS.

Cyanidin-3-glucoside attenuates 4-hydroxynonenal- and visible light-induced retinal damage in vitro and in vivo.

4-Hydroxynonenal (HNE) is a highly reactive end-product of lipid peroxidation reaction that leads to retinal pigment epithelial (RPE) cell damage. Cyanidin-3-glucoside (C3G), the most abundant anthocyanin in the edible parts of plants, is a nutritional supplement used for preventing retinal damage. However, the protective effect of C3G against HNE-induced RPE cell damage remains to be elucidated. The protective mechanisms of C3G on ARPE-19 cells after HNE exposure were investigated in this study. Results showed that compared with HNE-treated cells, the viability of ARPE-19 cells was significantly (P < 0.05) increased after 1 and 5 µM C3G treatment. C3G exhibited a significant (P < 0.05) inhibitory effect on the expression of senescence-associated ß-galactosidase in ARPE-19 cells. VEGF levels in the C3G groups were significantly (P < 0.05) decreased relative to those of the HNE-treated group. C3G also regulated the release of two inflammatory mediators, namely monocyte chemoattractant protein 1 and interleukine-8, in ARPE-19 cells after HNE treatment. Furthermore, C3G attenuated retinal cell apoptosis in pigmented rabbits induced by visible light. Therefore, our data showed that C3G has efficient protective effects on HNE-induced apoptosis, angiogenesis, and dysregulated cytokine production in ARPE-19 cells.

Genistein and daidzein induce apoptosis of colon cancer cells by inhibiting the accumulation of lipid droplets.

AIM: The purpose of this study was to investigate the possible mechanisms of genistein (GEN) and daidzein (DAI) in inducing apoptosis of colon cancer cells by inhibition of lipid droplets (LDs) accumulation. METHODS: HT-29 cells were used and treated by GEN or DAI in this paper. LDs accumulation was induced and inhibited by oleic acid (OA) and C75, respectively. The expression changes of LDs-related markers were confirmed by semiquantitative real time-PCR (RT-PCR), Western blotting, and immunofluorescence staining. RESULTS: GEN and DAI effectively reduced the LDs accumulation and downregulated the expression of Perilipin-1, ADRP and Tip-47 family proteins and vimentin levels. GEN and DAI significantly induced the mRNA expression of PPAR-γ, Fas, FABP, glycerol-3-phosphate acyltransferase (GPAT3), and microsomal TG transfer protein (MTTP), and reduced the mRNA expression of UCP2. Furthermore, the results showed a decrease of PI3K expression by GEN and DAI when compared with OA treatment, and both GEN and DAI can increase the expression of FOXO3a and caspase-8 significantly when these proteins were decreased by OA treatment. GEN is more effective than DAI in inducing cell apoptosis. CONCLUSION: Our results demonstrated that GEN and DAI inhibit the accumulation of LDs by regulating LDs-related factors and lead to a final apoptosis of colon cancer cells. These results may provide important new insights into the possible molecular mechanisms of isoflavones in anti-obesity and anti-tumor functions.

Fibrinolytic Therapy Improves Outcomes in Patients with Epidural Hematomas Following Cranioplasty: A Pilot Study.

BACKGROUND AND STUDY AIMS: Cranioplasty is a cosmetic procedure utilized to reconstruct cranial defects in patients following decompressive craniectomy. Epidural hematomas are a common complication of cranioplasty and often require surgical drainage. However, repeated surgery compromises patient safety and delays recovery. MATERIAL AND METHODS: We investigated the development of epidural hematomas among 131 patients who underwent cranioplasty. Then we explored the efficacy of urokinase (UK) injection for the noninvasive treatment of epidural hematomas. We observed that 15 patients presented with epidural hematoma following cranioplasty. UK (30,000 IU/3 mL) was injected into the hematoma cavity twice every 12 hours in the first postoperative day. Next we closed the subgaleal drain for 1.5 hours and connected it with a negative-pressure ball on full vacuum to allow drainage. Binary logistic regression analysis was used to evaluate the risk factors associated with the development of epidural hematomas. RESULTS: Our findings demonstrated that a sunken skin flap was a risk factor for epidural hematoma formation (p = 0.006). The decrease in epidural hematoma volume was 35.27 ± 7.27 mL in the first 12 hours on postoperative day 1 after UK treatment. All treated patients whose Glasgow Coma Scale score did not significantly change despite the epidural hematoma had an uneventful recovery without additional complications and were discharged from the hospital, except for one patient. CONCLUSION: Fibrinolytic therapy can be considered an optional treatment for postoperative epidural hematoma associated with cranioplasty, especially in patients who refused further operative treatment or who are not optimal candidates for a second surgery.

Genistein induces apoptosis of colon cancer cells by reversal of epithelial-to-mesenchymal via a Notch1/NF-κB/slug/E-cadherin pathway.

BACKGROUND: Genistein has been known to inhibit proliferation and induce apoptosis in several kinds of cancer cells. While knowledge of genistein in regulating epithelial mesenchymal transition (EMT) of colon cancer cells is unknown. METHODS: To investigate the effects and mechanisms of genistein on EMT of colon cancer cells, HT-29 cells were used and treated by genistein and TNF-α in this paper. EMT was determined by cell invasion assays using a transwell chamber and the expression changes of EMT-related markers were confirmed by RT-PCR, Western blotting, and immunofluorescence staining. RESULTS: Genistein inhibited cell migration at 200 µmol/L. Genistein reversed the EMT of colon cancer cells by upregulation of E-cadherin and downregulation of N-cadherin, accompanied by the suppression of EMT related makers, such as Snail2/slug, ZEB1, ZEB2, FOXC1, FOXC2 and TWIST1. Moreover, genistein can inhibit the expression of notch-1, p-NF-κB and NF-κB, while promote the expression of Bax/Bcl-2 and caspase-3 in HT-29 cells. CONCLUSION: The present study demonstrated that genistein suppressed the migration of colon cancer cells by reversal the EMT via suppressing the Notch1/NF-κB/slug/E-cadherin pathway. Genistein may be developed as a potential antimetastasis agent to colon cancer.

The protective effect of a buckwheat-enriched diet on renal injury in high salt-induced hypertension in rats.

An excess of dietary salt is the most common factor that contributes to the pathogenesis of hypertension. Dietary management is deemed critical to prevent and treat hypertension. We aimed at evaluating the preventive effect of the buckwheat (BW)-enriched diet on high salt-induced elevation of blood pressure (BP) and renal injury in order to provide a new focus on the design of strategies to prevent hypertension. Control, high salt (HS)-treated (8%), HS + tartary buckwheat (TB) (8% HS + 15% TB), and a group of HS + common buckwheat (CB) (8% HS + 15% CB) rats were used for 7 weeks. BP was monitored periodically during the study by the tail cuff method. HS intake caused a significant increase of BP, the level of serum Na(+) compared to the control group. BW significantly prevented the increase of BP, attenuated oxidative damage, and improved Na(+)/K(+)-ATPase activity in HS treated rats. These results show that a diet supplemented with whole BW has beneficial effects on hypertension, by decreasing blood pressure values and oxidative stress.

Inhibitory effect on HT-29 colon cancer cells of a water-soluble polysaccharide obtained from highland barley.

A water-soluble polysaccharide (BP-1) was obtained from highland barley (Hordeum vulgare L.) by hot water extraction and purification of sepharose column chromatography. BP-1 had an average molecular weight of about 6.7×104Da and was composed of glucose (Glc), xylose (Xyl), arabinose (Ara) and rhamnose (Rha) with a relative molar ratio of 8.82:1.92:1.50:1.00. It was found that BP-1 inhibited proliferation of human colon cancer cells (HT-29) in a time- and dose-dependent manner with half maximal inhibitory concentration at 48h of 48.18µg/mL. Western blotting results showed that BP-1 enhanced the phosphorylation of c-Jun N-terminal kinase (JNK), processes associated with the reactive oxygen species (ROS) formation and inhibited nuclear factor-κB (NF-κB) translocation from cytoplasm into nucleus. Meanwhile, the BP-1-induced apoptosis was related to the regulation of apoptosis-associated proteins, such as B-cell lymphoma-2 (Bcl-2), release of cytochrome C from mitochondria to cytoplasm and activation of caspase-8 and caspase-9. These results suggest that BP-1-induced HT-29 apoptosis through ROS-JNK and NF-κB-mediated caspase pathways.

Eicosapentaenoic acid (EPA) induced apoptosis in HepG2 cells through ROS-Ca(2+)-JNK mitochondrial pathways.

Eicosapentaenoic acid (EPA), a well-known dietary n-3 PUFAS, has been considered to inhibit proliferation of tumor cells. However, the molecular mechanism related to EPA-induced liver cancer cells apoptosis has not been reported. In this study, we investigated the effect of EPA on HepG2 cells proliferation and apoptosis mechanism through mitochondrial pathways. EPA inhibited proliferation of HepG2 cells in a dose-dependent manner and had no significant effect on the cell viability of humor normal liver L-02 cells. It was found that EPA initially evoked ROS formation, leading to [Ca(2+)]c accumulation and the mitochondrial permeability transition pore (MPTP) opening; EPA-induced HepG2 cells apoptosis was inhibited by N-acetylcysteine (NAC, an inhibitor of ROS), 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM, a chelator of calcium) and CsA (inhibitor of MPTP). The relationship between ROS production, the increase of cytoplasmic Ca and MPTP opening was detected. It seems that ROS may act as an upstream regulator of EPA-induced [Ca(2+)]c generation, moreover, generation of ROS, overload of mitochondrial [Ca(2+)]c, and JNK activated cause the opening of MPTP. Western blotting results showed that EPA elevated the phosphorylation status of JNK, processes associated with the ROS generation. Simultaneously, the apoptosis induced by EPA was related to release of cytochrome C from mitochondria to cytoplasm through the MPTP and activation of caspase-9 and caspase-3. These results suggest that EPA induces apoptosis through ROS-Ca(2+)-JNK mitochondrial pathways.

FOXO3 growth inhibition of colonic cells is dependent on intraepithelial lipid droplet density.

Forkhead transcription factor FOXO3 plays a critical role in suppressing tumor growth, in part, by increasing the cell cycle inhibitor p27kip1, and Foxo3 deficiency in mice results in marked colonic epithelial proliferation. Here, we show in Foxo3-deficient colonic epithelial cells a striking increase in intracytoplasmic lipid droplets (LDs), a dynamic organelle recently observed in human tumor tissue. Although the regulation and function of LDs in non-adipocytes is unclear, we hypothesize that the anti-proliferative effect of FOXO3 was dependent on lowering LD density, thus decreasing fuel energy in both normal and colon cancer cells. In mouse colonic tumors, we found an increased expression of LD coat protein PLIN2 compared with normal colonic epithelial cells. Stimulation of LD density in human colon cancer cells led to a PI3K-dependent loss of FOXO3 and a decrease in the negative regulator of lipid metabolism in Sirtuin6 (SIRT6). Foxo3 deficiency also led to a decrease in SIRT6, revealing the existence of LD and FOXO3 feedback regulation in colonic cells. In parallel, LD-dependent loss of FOXO3 led to its dissociation from the promoter and decreased expression of the cell cycle inhibitor p27kip1. Stimulation of LD density promoted proliferation in colon cancer cells, whereas silencing PLIN2 or overexpression of FOXO3 inhibited proliferation. Taken together, FOXO3 and LDs might serve as new targets for therapeutic intervention of colon cancer.

Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity.

BACKGROUND: Soy consumption is associated with a lower incidence of colon cancer which is believed to be mediated by one of its of components, genistein. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation of colon cancer cells plays an important role in colon cancer progression and is mediated by loss of tumor suppressor FOXO3 activity. The aim of this study was to assess if genistein exerts anti-proliferative properties by attenuating the negative effect of EGF on FOXO3 activity. METHODS: The effect of genistein on proliferation stimulated by EGF-mediated loss of FOXO3 was examined in human colonic cancer HT-29 cells. EGF-induced FOXO3 phosphorylation and translocation were assessed in the presence of genistein. EGF-mediated loss of FOXO3 interactions with p53 (co-immunoprecipitation) and promoter of p27kip1 (ChIP assay) were examined in presence of genistein in cells with mutated p53 (HT-29) and wild type p53 (HCT116). Silencing of p53 determined activity of FOXO3 when it is bound to p53. RESULTS: Genistein inhibited EGF-induced proliferation, while favoring dephosphorylation and nuclear retention of FOXO3 (active state) in colon cancer cells. Upstream of FOXO3, genistein acts via the PI3K/Akt pathway to inhibit EGF-stimulated FOXO3 phosphorylation (i.e. favors active state). Downstream, EGF-induced disassociation of FOXO3 from mutated tumor suppressor p53, but not wild type p53, is inhibited by genistein favoring FOXO3-p53(mut) interactions with the promoter of the cell cycle inhibitor p27kip1 in colon cancer cells. Thus, the FOXO3-p53(mut) complex leads to elevated p27kip1 expression and promotes cell cycle arrest. CONCLUSION: These novel anti-proliferative mechanisms of genistein suggest a possible role of combining genistein with other chemoreceptive agents for the treatment of colon cancer.

Tumor suppressor FOXO3 mediates signals from the EGF receptor to regulate proliferation of colonic cells.

Epithelial proliferation, critical for homeostasis, healing, and colon cancer progression, is in part controlled by epidermal growth factor receptor (EGFR). Proliferation of colonic epithelia can be induced by Citrobacter rodentium infection, and we have demonstrated that activity of tumor suppressor FOXO3 was attenuated after this infection. Thus the aim of this study was to determine the contribution of FOXO3 in EGFR-dependent proliferation of intestinal epithelia and colon cancer cell lines. In this study we show that, during infection with C. rodentium, EGFR was significantly phosphorylated in colonic mucosa and Foxo3 deficiency in this model lead to an increased number of bromodeoxyuridine-positive cells. In vitro, in human colon cancer cells, increased expression and activation of EGFR was associated with proliferation that leads to FOXO3 phosphorylation (inactivation). Following EGFR activation, FOXO3 was phosphorylated (via phosphatidylinositol 3-kinase/Akt) and translocated to the cytosol where it was degraded. Moreover, inhibition of proliferation by overexpressing FOXO3 was not reversed by the EGFR signaling, implicating FOXO3 as one of the regulators downstream of EGFR. FOXO3 binding to the promoter of the cell cycle inhibitor p27kip1 was decreased by EGFR signaling, suggesting its role in EGFR-dependent proliferation. In conclusion, we show that proliferation in colonic epithelia and colon cancer cells, stimulated by EGFR, is mediated via loss of FOXO3 activity and speculate that FOXO3 may serve as a target in the development of new pharmacological treatments of proliferative diseases.

Tumor suppressor FOXO3 participates in the regulation of intestinal inflammation.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic mucosal injury and the infiltration of inflammatory cells. Tumor suppressor FOXO3 regulates gene expression and its translocation to the cytosol leads to the abrogation of its transcriptional function. We have previously shown that bacterial infection regulates FOXO3 in intestinal epithelial cells and increases cytokine levels. As TNFalpha is a major contributor in intestinal inflammation, the aim of this study was to assess its effect on FOXO3 and FOXO3's contribution to intestinal inflammation in vitro and in vivo. TNFalpha induces the translocation of nuclear FOXO3 into the cytosol where it undergoes proteasomal degradation in human intestinal HT-29 cells. Proximally, the PI3K and IKK pathways mediate TNFalpha-induced FOXO3 phosphorylation. In FOXO3-silenced HT-29 cells, TNFalpha-induced IL-8 expression is increased approximately 83%. In vivo, Foxo3 is present in the nuclei and cytosol of colonic crypt epithelia. In DSS-induced colonic inflammation, Foxo3's nuclear localization is lost and it is only found in the cytosol. Consistent with a role for Foxo3 in colitis, Foxo3-deficient mice treated with DSS developed more severe colonic inflammation with an increased number of intraepithelial lymphocytes and PMNs infiltrated in the epithelia, than wild-type mice. In summary, TNFalpha inactivates FOXO3 in intestinal epithelia through the PI3K and IKK pathways and FOXO3 inactivation leads to the upregulation of IL-8 in vitro; in vivo Foxo3 is in the cytosol of inflamed colonic epithelia and Foxo3 deficiency leads to severe intestinal inflammation.

K562 cell growth activity and metabolism characteristics in APA microencapsulated culture and modeling study.

Cell microencapsulation is likely to play a major role in cell and transplantation therapies in the next decade. The microcapsules provide a special microenvironment in which cells always have different behaviors compared with free non-encapsulated culture. In this work, the behaviors of K562 leukemia cells were studied once entrapped in solid and liquefied APA microcapsules as well as in free non-encapsulated culture. Glucose pulse culture was employed to characterize the growth and metabolism of microencapsulated K562 cells. And mathematical modeling was presented to develop a basis for the deeper understanding of cells responses to different culture environments. Based on the results of experiments and modeling, it was found that cells presented a better growing pattern and maintain the activity at a higher level for extending time. The concentration of lactate was higher in solid microcapsules culture than that of liquefied microcapsules culture, but the cell number was lower. And the lactate yield coefficients (lactate/glucose) were 0.8129, 0.6978 and 0.601 for free non-encapsulated, solid microcapsules and liquefied microcapsules culture, respectively. An increase of glucose concentration led a decrease of cell activity, The glucose consumption ratio were 99.9%, 86.8%, 49.4% and 28.6% with the decrease in its concentration from 2 to 4, 6, 10 g/L, however, the lactate yield coefficient were 0.7184, 0.6654, 0.8239 and 0.9693, respectively.

[Characteristics of cell cycle and metabolism in microencapsulated K562 cell culture].

Human K562 leukemia cells were cultured under free and microencapsulated condition, respectively. The cell cycles in the two kinds of cultures were investigated by flow cytometry. Moreover, mathematical model was established to simulate the cell viability and metabolized characteristic in different cultures. It was found that the cell percent in S phase was higher and the cell viability was better when cultured in microcapsule than that in free culture. The results showed that the model successfully described the substrate consumption and product formation in microencapsulated culture as well as in suspension culture. Based on the model, it was indicated that not only there was a higher proliferation and metabolic activity but also the time of the high activity could keep longer in microencapsulated culture. The parameters of the model showed that there was no significant difference between the two kinds of cultures when the influence of the glucose on the cell viability was concerned (kA(free) approximately = kA (APA)) but lactate had a obvious suppression effect on cell viability in free culture, and neglectable suppression in microencapsulated culture (kL(free) > kL(APA)).