Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide

Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.

Malakoplakia of the esophagus caused by human papillomavirus infection

Malakoplakia is a rare granulomatous disease probably caused by infection and characterized histologically by Michaelis-Gutmann bodies.We report a more rarely seen case esophageal malakoplakia in a 54-year-old woman.She presented with coughing while eating and drinking.Gastroscopy showed yellow nodules in the esophagus,and endoscopic ultrasonography showed a space-occupying lesion in the substratum of the esophageal mucosa.All findings highly resembled esophageal cancer.Histopathological examination finally indentified this space-occupying lesion as malakoplakia and not cancer.Immunohistochemistry showed that she had human papillomavirus(HPV) infection in the esophagus,which indicates that infection was responsible for the malakoplakia.This is believed to be the first case of malakoplakia in the esophagus,and more importantly,we established that HPV infection was the initiator of esophageal malakoplakia.

Au cluster anchored on TiO_(2)/Ti_(3)C_(2) hybrid composites for efficient photocatalytic CO_(2) reduction

The size of metal nanoparticles is a key factor to enhance the photocatalytic activity of photocatalysts.However,the mechanism of this factor to the improvement of photocatalytic CO_(2) reduction performance is still unclear.Here,Au cluster/TiO_(2)/Ti_(3)C_(2) and Au nanoparticle/TiO_(2)/Ti_(3)C_(2) were successfully prepared by deposition-precipitation method.The experimental results show that the photocatalytic CO_(2) reduction performance of Au cluster/TiO_(2)/Ti_(3)C_(2) with quantum size effect is stronger than that of Au nanoparticle/TiO_(2)/Ti_(3)C_(2) with surface plasmon resonance.The enhanced photocatalytic CO_(2) reduction activity is assigned to the establishment of an overlapping orbital between the lowest unoccupied molecular orbital(LUMO)of the Au cluster and the anti-bonding orbital of CO_(2),which greatly promotes the activation efficiency of CO_(2).The existence of Au cluster and the mechanism of photocatalytic CO_(2) reduction performance were certified by high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM)and in situ Fourier transform infrared spectroscopy(ISFTIR).This work may open new opportunities for the establishment of stable and active metal nanocatalysts.

Spleen tyrosine kinase expression and its correlation with necrosis and high-risk histopathologic features in retinoblastoma

To the Editor:Retinoblastoma(RB)is the most common primary malignant intra-ocular tumor in children.It is thought to be initiated in response to biallelic RB1 inactivation and loss of functional RB protein.Spleen tyrosine kinase(SYK)plays different roles in the regulation of immunomodulatory signaling and cell proliferation in multiple malignancies,indicating either poor or favorable prognosis.A previous study showed that SYK is the fifth most significant gene and the only up-regulated kinase gene in RB according to the results derived from whole-genome sequencing,and SYK is also required for tumor cell survival.[1]However,the specific role of SYK in RB is still poorly understood.In this study,we examined SYK expression in RB and analyzed its relevance to necrosis and histopathologic high-risk factors(HRFs).