Study on β-TCP Coated Porous Mg as a Bone Tissue Engineering Scaffold Material

Three-dimensional honeycomb-structured magnesium （Mg） scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ- tricalcium phosphate （β-TCP） coatings were prepared on and the biodegradation mechanism was simply evaluated the porous Mg to further improve its biocompatibility, in vitro. It was found that the mechanical properties of this type of porous Mg significantly depended on its porosity. Elastic modulus and compressive strength similar to human bones could be obtained for the porous Mg with porosity of 42.6%-51%. It was observed that the human osteosarcoma cells （UMR106） were well adhered and proliferated on the surface of the β- TCP coated porous Mg, which indicates that theβ-TCP coated porous Mg is promising to be a bone tissue engineering scaffold material.

N-methyl-D-aspartate receptor subunit expression in memory-related brain areas of lead-exposed rats

Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced differences in NMDA subunit expression, and the correlation of lead poisoning with learning and memory, remain poorly understood. The present study measured differences in expression of NMDA receptor subunits NR1, NR2A, and NR2B in memory-related brain regions of rats who underwent different doses of lead exposure. Results demonstrated decreased NR1, NR2A, and NR2B subunit expressions in some memory-related brain areas. The inhibitory effect of 4.8 mmol/L lead exposure on hippocampal NR2B was most significant, although NR2A expression also significantly decreased following 14.4 mmol/L lead exposure. There was no difference in NR1 expression following exposure to 〈 4.8 mmol/L lead, although the inhibitory effect of 19.6 mmol/L lead exposure was strongest for NR1 expression in the hippocampus. Inhibitory avoidance test results revealed that greater concentrations of lead exposure resulted in decreased learning and memory. Therefore, lead toxicity was dependent on NMDA receptor subunit composition, and NR1, NR2A, and NR2B expressions were associated with time and concentration of lead exposure.

The protective effects of Gastrodia elata Bl.decoction and Gastrodin on Acrylamide-induced DNA damage in mice

Acrylamide(AA)is ubiquitous in packaging materials,paints,cosmetics,food and drinking water.However,AA has obvious neurotoxicity,reproductive toxicity and carcinogenicity,which seriously endangers human health.As one of precious traditional Chinese medicines,Gastrodia elata Bl.has been mainly used to lower blood pressure and resist myocardial ischemia.However,the antioxidant activity of Gastrodia elata Bl.on AA-induced DNA damage has not been reported.We found that AA(25,30 and 50 mg/kg)could cause DNA damage and the damage was time/dose dependent.After AA administration,Tail moment,micronuclei formation rate,8-OHdG and MDA level were significantly increased and SOD activity was decreased.Gastrodia elata Bl.decoction,gastrodin and vitamin C could reduce AA-induced DNA damage by decreasing AA-induced increment of tail moment and micronuclei formation rate.What’s more,Gastrodia elata Bl.decoction,gastrodin and vitamin C could lower 8-OHdG and MDA level and improve SOD activity.In conclusion,our research showed that Gastrodia elata Bl.decoction and gastrodin had protective effects on AA-induced DNA damage,and the potential protective mechanism might be related to anti-oxidative stress.

A review:anticancer activity of grape seed proanthocyanidins

For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human health.Indeed,GSPs have demonstrated substantial health benefi ts for a variety of disorders such as cancer,atherosclerosis,and cardiovascular diseases,to just name a few.In particular,GSPs inhibit cell proliferation,migration and invasion,and induce apoptosis and cell cycle arrest in various human cancers,including head and neck carcinoma,gastrointestinal tumors,lung cancer,skin tumors,and reproductive tumors,which points them to be promising chemo-preventive and/or chemotherapeutic agents.In this setting,we summarized the eff ects of GSPs against various types of cancer with a focus on the detailed molecular mechanisms involving various signaling pathways of tumor cells,which may serve as a basis for development of improved chemo-preventive or therapeutic strategies for cancer.

Inula britannica ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway

Objective: Inula britannica is a traditional Chinese medicinal and functional food with various effects such as anti-liver injury, hypoglycemia, antioxidants, and anti-tumor. The aim of this study was to investigate the protective effects and mechanisms of the ethanolic extract of I. britannica(EEIB) on alcohol-induced liver injury in mice.Methods: Fifty-six female C57BL/6 mice were randomly divided into seven groups: control group(Con),ethanol feeding model group(EtOH), Silibinin positive treatment group(EtOH + Silibinin 100 mg/kg),EEIB treatment group(EtOH + EEIB 100, 200, and 400 mg/kg), and EEIB control group(EEIB 400 mg/kg). The National Institute on Alcohol Abuse and Alcoholism(NIAAA) ethanol-feeding model was used to study the effects of EEIB on alcohol-induced lipid metabolism, inflammation, oxidative stress, and fibril formation in mice by histopathological evaluation, immunofluorescence staining, Western blotting analysis and molecular docking.Results: EEIB reduced liver indices to different degrees to normal levels and improved liver morphology in mice. EEIB inhibited alcohol-induced liver injury by activating the sirtuin 1(SIRT1)-adenosine monophosphate-activated protein kinase(AMPK) signaling pathway in the liver of alcohol-fed mice, in which sesquiterpenes may be the potential active ingredients, and also down-regulated the expression of alpha-smooth muscle actin(a-SMA), collagen alpha(Collagen I), tumor necrosis factor-alpha(TNFa) and attenuated alcohol-induced liver injury. In addition, EEIB also activated the nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway, which alleviated alcohol-induced liver injury at the level of oxidative stress. Notably, the EEIB control group demonstrated that EEIB had no toxic effects in mice. EEIB reduced alcoholic liver injury in a dose-dependent manner. Its therapeutic efficacy was comparable to, if not better than, that of Silibinin when administered at a dose of 400 mg/kg.Conclusion: EEIB showed significant therapeutic effects on alcohol-induced liver injury in mice, and its mechanism of action was related to the SIRT1-AMPK, nuclear factor-kappa B(NF-κB), and Nrf2 signaling pathways, in which sesquiterpenes may be the potential active ingredients.

DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer

DNMT3A encodes a DNA methyltransferase involved in development,cell differentiation,and gene transcription,which is mutated and aberrant-expressed in cancers.Here,we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer.Based on the epigenetic inhibitor library synthetic lethal screening,we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells.Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells.However,sensitive cells became resistant when DNMT3A was rescued.Furthermore,the selectivity to HDAC6 inhibition was recapitulated in mice,where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells.Mechanistically,DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding.Notably,our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition.Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6.Interestingly,HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells.These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers.Together,our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

Cognitive impairment caused by chronic cerebral hypoperfusion(CCH)is associated with white matter injury(WMI),possibly through the alteration of autophagy.Here,the autophagy—lysosomal pathway(ALP)dysfunction in white matter(WM)and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion(2VO).The results showed that cognitive impairment occurred by the 28th day after 2VO.Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day.By the 14th day,abnormal accumulation of autophagy substrate,lysosomal dysfunction,and the activation of mechanistic target of rapamycin(MTOR)pathway were observed in WM,paralleled with mature oligodendrocyte death.This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction.To target the ALP dysfunction,enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1(BECN1)in oligodendrocytes reduced mature oligodendrocyte death,and subsequently alleviated the WMI and cognitive impairment after CCH.These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO,which was associated with the aggravation of WMI and cognitive impairment.This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.