Epidural Co-Administration of Dexmedetomidine and Levobupivacaine Improves the Gastrointestinal Motility Function after Colonic Resection in Comparison to Co-Administration of Morphine and Levobupivacaine

Gastrointestinal motility may be impaired after intestinal surgery. Epidural morphine is effective in controlling postoperative pain, but can further reduce gastrointestinal motility. Here, we aimed to investigate the effects of epidural dexmedetomidine on gastrointestinal motility in patients undergoing colonic resection. Seventy-four patients undergoing colonic resection were enrolled in this clinical trial and allocated randomly to treatment with dexmedetomidine (D group) or morphine (M group). The D group received a loading dose epidural administration of 3 ml dexmedetomidine (0.5 μg kg^-1) and then a continuous epidural administration of 80 μg dexmedetomidine in 150 ml levobupivacaine (0.125%) at 3 ml h^-1 for two days. The M group received a loading dose epidural administration of 3 ml morphine (0.03 mg kg^-1) and then a continuous epidural administration of 4.5 mg morphine in 150 ml levobupivacaine at 3 ml h^-1 for two days. Verbal rating score (VRS), postoperative analgesic requirements, side effects related to analgesia, the time to postoperative first flatus (FFL) and first feces (FFE) were recorded. VRS and postoperative analgesic requirements were not significantly different between treatment groups. In contrast, the time to FFL and time to FFE were significant longer in M group in comparison to D group (P < 0.05). Moreover, patients in M group had a significantly higher incidence of nausea, vomiting, and pruritus (P < 0.05). No patients showed neurologic deficits in either group. In comparison to morphine, epidural dexmedetomidine is safe and beneficial for the recovery of gastrointestinal motility after colonic resection when used as an adjunct with levobupivacaine for postoperative pain control.

Trial Registration

Chinese Clinical Trial Registry ChiCTR-TRC-14004644     

Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways

Oxidative damage and inflammation are closely associated with the pathogenesis of acute lung injury (ALI). Thus, we explored the protective effect of isovitexin (IV), a glycosylflavonoid, in the context of ALI. To accomplish this, we created in vitro and in vivo models by respectively exposing macrophages to lipopolysaccharide (LPS) and using LPS to induce ALI in mice. In vitro, our results showed that IV treatment reduced LPS-induced pro-inflammatory cytokine secretion, iNOS and COX-2 expression and decreased the generation of ROS. Consistent findings were obtained in vivo. Additionally, IV inhibited H₂O₂-induced cytotoxicity and apoptosis. However, these effects were partially reversed following the use of an HO-1 inhibitor in vitro. Further studies revealed that IV significantly inhibited MAPK phosphorylation, reduced NF-κB nuclear translocation, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in RAW 264.7 cells. In vivo, pretreatment with IV attenuated histopathological changes, infiltration of polymorphonuclear granulocytes and endothelial activation, decreased the expression of ICAM-1 and VCAM-1, reduced the levels of MPO and MDA, and increased the content of GSH and SOD in ALI. Furthermore, IV treatment effectively increased Nrf2 and HO-1 expression in lung tissues. Therefore, IV may offer a protective role against LPS-induced ALI by inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways.     

FBXL10 regulates cardiac dysfunction in diabetic cardiomyopathy via the PKC β2 pathway

Diabetic cardiomyopathy (DCM) is a condition associated with significant structural changes including cardiac tissue necrosis, localized fibrosis, and cardiomyocyte hypertrophy. This study sought to assess whether and how FBXL10 can attenuate DCM using a rat streptozotocin (STZ)‐induced DCM model system. In the current study, we found that FBXL10 expression was significantly decreased in diabetic rat hearts. FBXL10 protected cells from high glucose (HG)‐induced inflammation, oxidative stress, and apoptosis in vitro. In addition, FBXL10 significantly activated PKC β2 signaling pathway in H9c2 cells and rat model. The cardiomyocyte‐specific overexpression of FBXL10 at 12 weeks after the initial STZ administration attenuated oxidative stress and inflammation, thereby reducing cardiomyocyte death and preserving cardiac function in these animals. Moreover, FBXL10 protected against DCM via activation of the PKC β2 pathway. In conclusion, FBXL has the therapeutic potential for the treatment of DCM.     

Berberine attenuates XRCC1‐mediated base excision repair and sensitizes breast cancer cells to the chemotherapeutic drugs

Berberine (BBR) is a natural isoquinoline alkaloid, which is used in traditional medicine for its anti‐microbial, anti‐protozoal, anti‐diarrhoeal activities. Berberine interacts with DNA and displays anti‐cancer activities, yet its effects on cellular DNA repair and on synthetic treatments with chemotherapeutic drugs remain unclear. In this study, we investigated the effects of BBR on DNA repair and on sensitization of breast cancer cells to different types of DNA damage anti‐tumoural drugs. We found BBR arrested cells in the cell cycle S phase and induced DNA breaks. Cell growth analysis showed BBR sensitized MDA‐MB‐231 cells to cisplatin, camptothecin and methyl methanesulfonate; however, BBR had no synergistic effects with hydroxurea and olaparib. These results suggest BBR only affects specific DNA repair pathways. Western blot showed BBR down‐regulated XRCC1 expressions, and the rescued XRCC1 recovered the resistance of cancer cells to BBR. Therefore, we conclude that BBR interferes with XRCC1‐mediated base excision repair to sensitize cancer cells to chemotherapeutic drugs. These finding can contribute to understanding the effects of BBR on cellular DNA repair and the clinical employment of BBR in treatment of breast cancer.     

Confined Fe2VO4⊂Nitrogen‐Doped Carbon Nanowires with Internal Void Space for High‐Rate and Ultrastable Potassium‐Ion Storage

Developing low‐cost, high‐capacity, high‐rate, and robust earth‐abundant electrode materials for energy storage is critical for the practical and scalable application of advanced battery technologies. Herein, the first example of synthesizing 1D peapod‐like bimetallic Fe₂VO₄ nanorods confined in N‐doped carbon porous nanowires with internal void space (Fe₂VO₄?NC nanopeapods) as a high‐capacity and stable anode material for potassium‐ion batteries (KIBs) is reported. The peapod‐like Fe₂VO₄?NC nanopeapod heterostructures with interior void space and external carbon shell efficiently prevent the aggregation of the active materials, facilitate fast transportation of electrons and ions, and accommodate volume variation during the cycling process, which substantially boosts the rate and cycling performance of Fe₂VO₄. The Fe₂VO₄?NC electrode exhibits high reversible specific depotassiation capacity of 380 mAh g^?1 at 100 mA g^?1 after 60 cycles and remarkable rate capability as well as long cycling stability with a high capacity of 196 mAh g^?1 at 4 A g^?1 after 2300 cycles. The first‐principles calculations reveal that Fe₂VO₄?NC nanopeapods have high ionic/electronic conductivity characteristics and low diffusion barriers for K⁺‐intercalation. This study opens up new way for investigating high‐capacity metal oxide as high‐rate and robust electrode materials for KIBs.