The gene PFKFB3 encodes for inducible 6-phosphofructo-2-kinase, a glycolysis-regulatory enzyme that protects against diet-induced intestine inflammation. However, it is unclear how nutrient overload regulates PFKFB3 expression and inflammatory responses in intestinal epithelial cells (IECs). In the present study, primary IECs were isolated from small intestine of C57BL/6J mice fed a low-fat diet (LFD) or high-fat diet (HFD) for 12 weeks. Additionally, CMT-93 cells, a cell line for IECs, were cultured in low glucose (LG, 5.5 mmol/L) or high glucose (HG, 27.5 mmol/L) medium and treated with palmitate (50 μmol/L) or bovine serum albumin (BSA) for 24 hr. These cells were analyzed for PFKFB3 and inflammatory markers. Compared with LFD, HFD feeding decreased IEC PFKFB3 expression and increased IEC proinflammatory responses. In CMT-93 cells, HG significantly increased PFKFB3 expression and proinflammatory responses compared with LG. Interestingly, palmitate decreased PFKFB3 expression and increased proinflammatory responses compared with BSA, regardless of glucose concentrations. Furthermore, HG significantly increased PFKFB3 promoter transcription activity compared with LG. Upon PFKFB3 overexpression, proinflammatory responses in CMT-93 cells were decreased. Taken together, these results indicate that in IECs glucose stimulates PFKFB3 expression and palmitate contributes to increased proinflammatory responses. Therefore, PFKFB3 regulates IEC inflammatory status in response to macronutrients.
Adjuvants play an important role in enhancing vaccine‐induced immune protection. Adequate cellular uptake, robust lysosomal escape, and subsequent antigen cross‐presentation are critical steps for vaccine adjuvants to effectively elicit cellular immunity. Here, a fluorinated supramolecular strategy to generate a series of peptide adjuvants by using arginine (R) and fluorinated diphenylalanine peptide (DP) is adopted. It is found that the self‐assembly ability and antigen‐binding affinity of these adjuvants increase with the number of fluorine (F) and can be regulated by R. By comparison, 4RDP(F5) shows the strongest binding affinity with model antigen ovalbumin (OVA) and the best performance in dendritic cells maturation and antigen's lysosomal escape, which contributes to the subsequent antigen cross‐presentation. As a consequence, 4RDP(F5)‐OVA nanovaccine generates a strong cellular immunity in a prophylactic OVA‐expressing EG7‐OVA lymphoma model, leading to long‐term immune memory for resisting tumor challenge. What's more, 4RDP(F5)‐OVA nanovaccine in combination with anti‐programmed cell death ligand‐1 (anti‐PD‐L1) checkpoint blockade could effectively elicit anti‐tumor immune responses and inhibit tumor growth in a therapeutic EG7‐OVA lymphoma model. Overall, this study demonstrates the simplicity and effectiveness of fluorinated supramolecular strategies for constructing adjuvants and might provide an attractive vaccine adjuvant candidate for cancer immunotherapy.
Background The unicameral bone cyst (UBC) is a kind of benign tumor whose clinical treatments and efficacy are controversial. The purpose of this study was to evaluate the efficacy of the elastic stable intramedullary nail (ESIN), the injection of autologous bone marrow (ABM), and the combination of ESIN and ABM in the treatment of bone cyst in children. Methods Eighty-three cases with simple bone cyst were analyzed retrospectively. Twenty-eight cases were treated with ABM. Twenty-eight cases were treated with ESIN. Twenty-seven cases were treated with ABM and ESIN. All cases were diagnosed through X-ray, CT, or MRI scans. For the suspicious ones, the pathological biopsy was performed for an accurate diagnosis. X-ray examinations were carried out for the postoperative follow-up. Capanna criteria for bone cyst was used for postoperative evaluation of three methods. Results All cases accomplished the follow-up. The effective rate of the ABM + ESIN group was significantly higher than that of the ABM group (P < 0.05), and the cure rates of the ESIN group and the ABM + ESIN group were higher than that of the ABM group (P < 0.05, respectively). The cure time in the ESIN group was lower than that of the other two groups (P < 0.05, respectively). The times for admission were 2.0 ± 0.0 in the ESIN group, 5.7 ± 1.9 in the ABM group, and 4.7 ± 2.4 in the ABM + ESIN group (P < 0.05 when compared with each other). Conclusions The method of ABM combined with ESIN for children’s bone cyst has the highest effective rate and curative rate. For the individual method, ESIN has a higher effective rate and curative rate than that of ABM. Meanwhile, it has the fewest time of hospitalization.
Personal exposure to PM associated with heavy metals were investigated at and around the same road by cycling, walking, taxi and bus in Tianjin, China. One trip on each mode was undertaken during 4 h of both morning and evening peak hours. Results of one-way analysis of variance (ANOVA) to compare mean concentrations of PM and each metal measured by four modes, the enrichment level of heavy metals in four modes and the carcinogenic, non-carcinogenic risk and probabilistic estimation of health risks of metals (Cr, Ni, Cu, Zn and Pb). Arithmetic means of PM personal exposure were 323.66, 313.37, 214.84 and 160.71 μg/m for cycling, walking, bus and taxi, which resulted from the difference of source (vehicle exhaust and road dust) of exposure to PM. Na has the highest concentration, followed by Al, Ca, K, Fe, Mg, Zn, Ni, Pb, Cu and Cr. The higher Na concentrations were observed in Tianjin in light of its major sea salt influence. The concentrations of Ca, Mg, Fe and Zn in four modes followed different orders, while other metals have no significant difference between four modes. Enrichment factors of metals in PM showed that some metals are enriched, ranging from contaminated to extremely contaminated, for example, Ni, Cu, Zn, Pb, Na and Cr. Others are barely enriched such as Ca, K, Mg and Fe. It illustrated the former is mainly effected by anthropogenic activates and the source of latter comes from crust. From the results of non-carcinogenic and carcinogenic risks of metals, the intake of metals with inhalation for 4 h by four modes did not pose a significant potential chronic-toxic risk and was an acceptable or tolerable risk at present. But uncertainty analysis of health risks showed there were 4.05 and 6.87% probability that make carcinogenic risk values to exceed 10 when male choose walking/cycling to work. Commuters' rush hour exposures were significantly influenced by mode of transport. We suggest that future work should focus on further research between heavy metals in PM exposure and its specific epidemiology effects.
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