Carboxylic graphene oxide‐composited polypyrrole/poly‐l‐lactic acid (C‐GO/PPy/PLLA) films were fabricated by electrochemical deposition of C‐GO‐composited PPy on PLLA fibers‐film, and their conductivity and tensile strength (∼4.6 S/cm and 26.4 MPa, respectively) were stably remained after the immersion of 4 weeks, due to the hydrogen bond interaction between graphene oxide's carboxylic groups and pyrrole's imino groups. Their specific surface areas of ∼57.5 m2/g and pore volume of ∼0.02 cm3/g were significantly larger than those of PPy/PLLA films, due to the addition of C‐GO nanosheets. Then, C‐GO/PPy/PLLA conducting conduit with 2 mm inner diameter was prepared to bridge 10 mm sciatic nerve defect of rats, and the direction of fiber‐axis in the conduit was the same as the conduit central axis. Electrical stimulation (ES) of 1 V and 20 Hz through the conducting conduit was exerted on the defect site. The results of in vivo electrophysiological and histological evaluation indicated that, the sciatic nerve defect could be repaired in C‐GO/PPy/PLLA conduit, moreover the re‐innervated gastrocnemius muscle and nerve conduction in C‐GO/PPy/PLLA conduit & ES group were obviously better than the conduit without ES group. The results of transmission electron microscope analysis also demonstrated that the mean thickness of myelin sheath and diameter of axon in C‐GO/PPy/PLLA conduit & ES group were significantly larger than those without ES, suggesting that the repair efficiency of ES & conduit group was closer to that of autograft group. These results indicated the great potential of C‐GO/PPy/PLLA with the in vivo ES in the application of sciatic nerve repair.

Intestinal mucositis is a common toxic side effect in cancer patients receiving high-dose chemotherapy. This study aimed to evaluate the beneficial effects of Bifidobacterium infantis in a rat model of intestinal mucositis induced by 5-fluorouracil (5-FU). Thirty male Sprague-Dawley rats were divided into three groups: control, 5-FU, and 5-FU + B. infantis. A single intraperitoneal injection of 5-FU (150 mg/kg) was used to induce intestinal mucositis. B. infantis (1×109 cfu) was administered for 11 days, starting from 7 days before 5-FU injection. Intestinal mucositis was evaluated based on body weight, villus height, immunohistological expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa beta (NF-κB), levels of the pro-inflammatory factors interleukin 1 beta and tumour necrosis factor alpha, and myeloperoxidase (MPO) concentration. The results showed that the 5-FU + B. infantis group demonstrated a higher body weight and villus height, increased expression of PCNA, reduced expression of NF-κB and pro-inflammatory factors, and lower MPO concentration compared to the 5-FU group. These data suggest that probiotic B. infantis is effective in reducing chemotherapy-induced intestinal mucositis in rats.

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Background The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma. Methods All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy. Results Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall. Conclusions There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.

Background and Purpose. Angong Niuhuang Wan (ANW) is a traditional Chinese herbal formula that has been widely used for the treatment of ischemic stroke, whereas its underlying therapeutic mechanism remains unclear. The objective of the study is to explore the main bioactive ingredients and interaction mechanism of ANW on ischemic stroke based on the network pharmacology method. Methods. The chemical ingredients of ANW were retrieved from TCMSP, TCMID, and literature. We predicted the potential targets of active ingredients by PubChem, Swiss Target Prediction, and STITCH databases. The targets related to ischemic stroke were retrieved using GeneCards, DisGeNET, DrugBank, TTD, and GEO databases. Subsequently, Venn diagrams were used to identify common targets of active ingredients and ischemic stroke. Protein-protein interaction (PPI) network was structured with STRING platform and Cytoscape 3.8.2. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of key targets were performed in the Metascape database. Finally, molecular docking was conducted by AutoDock Tools and PyMOL software. Results. A total of 2391 targets were identified for 230 active ingredients of ANW, and 1386 of them overlapped with ischemic stroke targets. The key active ingredients were mainly quercetin, β-estradiol, berberine, wogonin, and β-sitosterol, and the key targets were also identified, including IL-6, AKT1, MAPK3, PIK3CA, and TNF. The biological process (BP) results indicated that ANW may have therapeutic effects through response oxidative stress, inflammatory response, cellular response to lipid, and response to nutrient levels. Furthermore, the ingredients of ANW were predicted to have therapeutic effects on ischemic stroke via the HIF-1 signaling pathway, FoxO signaling pathway, chemokine signaling pathway, fluid shear stress and atherosclerosis, and neurotrophin signaling pathway. The molecular docking results all showed that the core ingredients were strong binding activity with the core targets. Conclusion. In conclusion, the bioinformatics and pharmacological results reveal that counteracting oxidative stress, suppressing inflammation, inhibiting the development of AS, and even protecting neurological function are critical pathways for ANW in the treatment of ischemic stroke. These results may help to elucidate the mechanism of ANW on ischemic stroke for experimental studies and clinical applications.

Eucommiae Cortex (EC), a rare, nourishing medicinal herb that is native in China, has good effect in the treatment of hypertension. In this study, we compared tissue distribution of six representative active components of EC extract—genipinic acid (GA), protocatechuic acid (PCA), neochlorogenic acid (NCA), chlorogenic acid (CA), (+)-pinoresinol di-O-β-D-glucopyranoside (PDG), and (+)-pinoresinol 4′-O-β-D-glucopyranoside (PG)—between normal rats and spontaneously hypertensive rats (SHRs). Each rat was intragastrically given EC extract at a dose of 5.4 g/kg. Rats were sacrificed at 10 min, 30 min, 2 h, and 8 h after administration; six rats were sacrificed at each time point. Then, we quickly harvested their major organs, including heart, liver, spleen, lungs, kidneys, and brain. Using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we determined the levels of the above mentioned six components in the organs of both types of rats and then analyzed differences in the tissue distribution. The results showed that levels of each component differed between SHRs and the normal group at each time point. As time progressed, the number of organs in which GA distribution in each tissue of SHRs differed from that of the normal group gradually increased: SHRs showed lower GA levels than normal rats. Levels of PG and PDG in both groups at 10 and 30 min were similar. NCA and CA in the SHR group and the normal group at 10 min, 30 min, and 2 h were also similar to some extent. The results indicated that the pathological state of spontaneous hypertension could affect tissue distribution of EC active components in rats.

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ObjectiveWe discussed the intensity of treadmill running on learning, memory and expression of cell cycle-related proteins in rats with cerebral ischemia.MethodEighty healthy male SD rats were randomly divided into normal group, model group, intensity I group and intensity II group, with 20 rats in each group. The four-vessel occlusion method of Pulsinelli (4-VO) was used to induce global cerebral ischemia. Brain neuronal morphology was observed by hematoxylin-eosin (HE) staining at 3h, 6h, 24h and 48h after modeling, respectively. Hippocampal expressions of cyclin A and cyclin E were detected by immunohistochemistry. At 48h after modeling, the learning and memory performance of rats was tested by water maze experiment.ResultCompared with the normal group, the other three groups had a significant reduction in surviving neurons, prolonging of escape latency and decreased number of passes over the former position of the platform (P<0.05). The number of surviving neurons and the number of passes over the former position of the platform were obviously lower in the model group than in intensity I group (P<0.05), but significantly higher compared with intensity II group (P<0.05). Escape latency of the model group was obviously prolonged as compared with intensity I group (P<0.05), but much shorter than that of intensity II group (P<0.05). Compared with the normal group, the expressions of cyclin A and cyclin E were significantly upregulated at different time points after modeling (P<0.05). The expression of the model group was higher than that of intensity I group, but lower than that of intensity II group (P<0.05).ConclusionModerate intensity of treadmill running can help protect brain neurons and improve learning and memory performance of rats with global cerebral ischemia. But high intensity of treadmill running has a negative impact, possibly through the regulation of cell cycle-related proteins in ischemia/reperfusion injury.