Abstract Background Diabetes induces central nervous system damage, leading to cognitive decline. Fibroblast growth factor 1 (FGF1) has dual function of neuroprotection and normalizing hyperglycemia. To date, the precise mechanisms and potential treating strategies of FGF1 for diabetes-induced cognitive decline (DICD) hasn’t been fully elucidated. Methods In this study, db/db mice were used as DICD animal model. We found that diabetes remarkably suppressed FGF1 expression in hippocampus. Thus, exogenous FGF1 had been treated for db/db mice and SH-SY5Y cells. Results FGF1 significantly ameliorates DICD with better spatial learning and memory function. Moreover, FGF1 blocked diabetes-induced morphological structure change, neuronal apoptosis and Aβ 1–42 deposition and synaptic dysfunction in hippocampus. But normalizing glucose may not the only contributed factor for FGF1 treating DICD with evidencing that metformin-treated db/db mice has a inferior cognitive function than that in FGF1 group. Current mechanistic study had found that diabetes inhibits cAMP-response element binding protein (CREB) activity and subsequently suppresses brain derived neurotrophic factor (BDNF) level via coordinately regulating PERK signaling and PI3K/AKT signaling in hippocampus, which were reversed by FGF1. Conclusion We conclude that FGF1 exerts its neuroprotective role and normalizing hyperglycemia effect, consequently ameliorates DICD, implying FGF1 holds a great promise to develop a new treatment for DICD.
KRAS (kirsten rat sarcoma viral oncogene) is a member of the RAS family. KRAS mutations are one of most dominant mutations in colorectal cancer (CRC). The impact of KRAS mutations on the prognosis and survival of CRC patients drives many research studies to explore potential therapeutics or target therapy for the KRAS mutant CRC. This review summarizes the current understanding of the pathological consequences of the KRAS mutations in the development of CRC; and the impact of the mutations on the response and the sensitivity to the current front-line chemotherapy. The current therapeutic strategies for treating KRAS mutant CRC, the difficulties and challenges will also be discussed.
Endothelial dysfunction plays key roles in the pathological process of contrast media (CM)-induced acute kidney injury (CI-AKI) in patients undergoing vascular angiography or intervention treatment. Previously, we have demonstrated that an apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, inhibits oxidative stress and improves endothelial dysfunction caused by CM through the AMPK/PKC pathway. However, it is unclear whether CM induce metabolic impairments in endothelial cells and whether D-4F ameliorates these metabolic impairments. In this work, we evaluated vitalities of human umbilical vein endothelial cells (HUVECs) treated with iodixanol and D-4F and performed nuclear magnetic resonance (NMR)-based metabolomic analysis to assess iodixanol-induced metabolic impairments in HUVECs, and to address the metabolic mechanisms underlying the protective effects of D-4F for ameliorating these metabolic impairments. Our results showed that iodixanol treatment distinctly impaired the vitality of HUVECs, and greatly disordered the metabolic pathways related to energy production and oxidative stress. Iodixanol activated glucose metabolism and the TCA cycle but inhibited choline metabolism and glutathione metabolism. Significantly, D-4F pretreatment could improve the iodixanol-impaired vitality of HUVECs and ameliorate the iodixanol-induced impairments in several metabolic pathways including glycolysis, TCA cycle and choline metabolism in HUVECs. Moreover, D-4F upregulated the glutathione level and hence enhanced antioxidative capacity and increased the levels of tyrosine and nicotinamide adenine dinucleotide in HUVECs. These results provided the mechanistic understanding of CM-induced endothelial impairments and the protective effects of D-4F for improving endothelial cell dysfunction. This work is beneficial to further exploring D-4F as a potential pharmacological agent for preventing CM-induced endothelial impairment and acute kidney injury.
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Thermal distortion of tailored blanks (TBs) during welding usually leads to a poor formability in the subsequent plastic deformation of TBs, and the welding distortion becomes especially serious in TBs consisting of different thickness plates. In this investigation, finite element method was applied to investigate the welding distortion of TBs with different thickness plates produced by laser beam welding. At the beginning, a 3D heat source model was built and verified by experimental results. Then, the following simulation results showed that the residual stresses generated in the thick plate side of the TBs were higher than those in the thin one. The varied reduction of heat input along the thickness direction for those two base plates can explain for this.
Brusatol is a butyrolactone compound isolated from traditional Chinese medicine Brucea javanica . It has been reported to possess strong cytotoxicity against various cancer cells, thus showing its potential as an anticancer drug. Besides, lipopolysaccharide (LPS) plays a central role in the tumor microenvironment, while epithelial-mesenchymal transformation (EMT), a biological process by which epithelial cells are transformed into mesenchymal phenotypic cells through specific procedures, participates in chronic inflammation and tumor metastasis. This study aimed to investigate the inhibition of LPS-induced tumor cell invasion and metastasis and the molecular mechanism of apoptosis induced by brusatol in human gastric cancer SGC-7901 cells. Cell viability, cell migration and invasion ability, inflammatory factor release, and protein expression were detected using methyl thiazolyl tetrazolium assays, transwell assays, ELISA kit, and Western blot analysis, respectively. The change of EMT marker protein vimentin was assessed using immunofluorescence, while the apoptosis rate was measured using flow cytometry. In summary, brusatol inhibited LPS-induced EMT via the deactivation of the PI3K/Akt/NF-кB signaling pathway. This provides a useful new theoretical basis for the treatment of gastric cancer in the future.
Aim To explore the clinic effect of locking plate internal fixation and callus-grafting on femur intercondylar comminuted fracture.Methods 17 cases of femur intercondylar comminuted fracture were treated with open reduction and internal fixation by locking plate and callus-grafting.By AO classification,11 cases were regarded as C2,6 cases C3.The knee jiont's function exercises of all the cases begun gradually on the fourth day after operation.Results All the cases were followed up for 6 months to 2 years after operation.All the fracture healed in 3 to 6 months.According to Merchan's knee function score system,10 knees were rated as excellent,5 good,and 3 fair.The total good and excellent rate was 88.2%.Conclusion Locking plate internal fixation and callus-grafting are satisfiactory in treatment of femur intercondylar comminuted fracture.This mothod owns merits of fast bone healing,steady fixation and good knee jiont function.
Objective To explore the possible causes resulting in stiffness in knee joint post-operation of femur intercondylar fracture.Methods Twenty-three cases dignosed as knee joint stiffness were retrospectively analyzed and possible causes were discussed.Results According to Merchan' knee function score system,there were 18 fair and 5 poor.Operation approaches in 20 cases were regarded improper,knee joint capsules were eligibly not reconstructed in 19 cases;unfit choice of internal fixation materials emerged in 10 cases,plates and scrows for inernal fixation were broken in 4 cases,and overtime external fixation was applied in 4 cases.Conclusion Knee joint stiffness after operation of femur intercondylar fracture occurred easily.In order to avoid it proper operating approach and internal fixation materials were important.Knee joint capsule needed to be reconstructed.Postoperative drainage and early function exercise should actively be done.
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