Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

Design and comparison of hybrid multi-bend achromat lattices for HALF storage ring

The Hefei Advanced Light Facility(HALF)proposed by the National Synchrotron Radiation Laboratory is a green-field vacuum ultraviolet and soft X-ray diffraction-limited storage ring light source with a beam energy of 2.2 GeV and emittance goal of less than 100 pm rad.Inspired by the ESRF-EBS hybrid multi-bend achromat(HMBA),SLS-2,and Diamond-II lattices,we have proposed and designed a modified H6BA lattice as the baseline lattice of the HALF storage ring with 20 identical cells and a natural emittance of approximately 86 pm rad.In this paper,three other types of HMBA lattices including two H7BA lattices and a H6BA lattice are designed for HALF with the same number of cells.The main storage ring proper-ties of these four HMBA lattices are compared.Because the intra-beam scattering(IBS)effect is significant in the HALF storage ring,we calculate and compare the equilibrium emittances of the four lattices with IBS included.These comparisons show that the present modified H6BA lattice,which has a relatively low equilibrium emittance and more straight sections,is preferred for the HALF storage ring after a comprehensive consideration.

Precipitation and evolution of nodular graphite during solidification process of ductile iron

The quantity and morphology of spheroidal graphite have an important effect on the properties of ductile iron, and the characteristics of spheroidal graphite are determined by the solidification process. The aim of this work is to explore the precipitation and evolution of graphite nodules in hypoeutectic, eutectic, and hypereutectic ductile irons by thermal analysis, liquid quenching and metallographic technique. Results show that hypoeutectic ductile iron has the longest solidification time and the lowest eutectic temperature;eutectic ductile iron has the shortest solidification time;hypereutectic ductile iron has the highest eutectic temperature. After solidification is completed, hypoeutectic ductile iron has the lowest nodule count, nodularity and graphite fraction;eutectic ductile iron has the highest nodule count, nodularity and the smallest nodule diameter;hypereutectic has the highest nodule diameter and graphite fraction. The nucleation and growth of graphite nodules in hypereutectic ductile iron starts before bulk eutectic crystallization stage, however, the precipitation and evolution of graphite nodules of hypoeutectic and eutectic ductile irons mainly occur in the eutectic crystallization stage. The graphite precipitated in eutectic crystallization of hypoeutectic, eutectic, and hypereutectic ductile irons, are 61%, 68% and 43% of total graphite volume fraction, respectively. Simultaneously, there are plenty of austenite dendrites in hypoeutectic and hypereutectic ductile irons, which are prone to shrinkage defects. Therefore, the eutectic ductile iron has the smallest shrinkage tendency.

Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly understood.AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.METHODS We measured the expression of lncRNA W42 in HCC tissues and cells(Huh7 and SMMC-7721)by quantitative reverse transcriptase polymerase chain reaction.Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression.HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42.Cell functions were detected by cell counting Kit-8(CCK-8),colony formation,flow cytometry and Transwell assays.The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays.An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo.The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.RESULTS In this study,we identified a novel lncRNA(lncRNA W42),and investigated its biological functions and clinical significance in HCC.LncRNA W42 expression was upregulated in HCC tissues and cells.Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC,and inhibited cell apoptosis.LncRNA W42 directly bound to DBN1 and activated the downstream pathway.LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo.The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42,which is upregulated in HCC,may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.

Long non-coding ribonucleic acid W5 inhibits progression and predicts favorable prognosis in hepatocellular carcinoma

BACKGROUND Accumulating evidence has revealed that several long non-coding ribonucleic acids(lncRNAs)are crucial in the progress of hepatocellular carcinoma(HCC).AIM To classify a long non-coding RNA,i.e.,lncRNA W5,and to determine the clinical significance and potential roles of lncRNA W5 in HCC.METHODS The results showed that lncRNA W5 expression was significantly downregulated in HCC cell lines and tissues.Analysis of the association between lncRNA W5 expression levels and clinicopathological features suggested that low lncRNA W5 expression was related to large tumor size(P<0.01),poor histological grade(P<0.05)and serious portal vein tumor thrombosis(P<0.05).Furthermore,Kaplan-Meier survival analysis showed that low expression of lncRNA W5 predicts poor overall survival(P=0.016).RESULTS Gain-of-loss function experiments,including cell counting kit8 assays,colony formation assays,and transwell assays,were performed in vitro to investigate thebiological roles of lncRNA W5.In vitro experiments showed that ectopic overexpression of lncRNA W5 suppressed HCC cell proliferation,migration and invasion;conversely,silencing of lncRNA W5 promoted cell proliferation,migration and invasion.In addition,acting as a tumor suppressor gene in HCC,lncRNA W5 inhibited the growth of HCC xenograft tumors in vivo.CONCLUSION These results showed that lncRNA W5 is down-regulated in HCC,and it may suppress HCC progression and predict poor clinical outcomes in patients with HCC.LncRNA W5 may serve as a potential HCC prognostic biomarker in addition to a therapeutic target.

Safety,immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly:a prospective longitudinal study

The safety and efficacy of COVID-19 vaccines in the elderly,a high-risk group for severe COVID-19 infection,have not been fully understood.To clarify these issues,this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety,immunogenicity,and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001.The results showed that this vaccination protocol was safe and tolerable in the elderly.After administering two doses of the BBIBP-CorV,the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals.After the ZF2001 booster dose,the antibody-positive rates in the elderly were comparable to those in the young;however,the antibody titers remained lower.Gender,age,and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals.The pseudovirus neutralization assay showed that,compared with those after receiving two doses of BBIBP-CorV priming,some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster.Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms.The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young.Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

Increased circulating level of interleukin-6 and CD8+T cell exhaustion are associated with progression of COVID-19

Background: Coronavirus disease 2019(COVID-19)is pandemic.It is critical to identify COVID-19 patients who are most likely to develop a severe disease.This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.Methods:: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing,China from December 27,2019 to March 12,2020 were enrolled in this study and followed-up to March 16,2020.Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by theχ2 test or the Fisher exact test(categorical variables)and independent group t test or Mann–Whitney U test(continuous variables).The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.Results: The mean incubation was 8.67(95%confidence interval,6.78–10.56)days.Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38(9.86–12.90)days.Compared to pneumonia-free patients,pneumonia patients were 16.5 years older and had higher frequencies of having hypertension,fever,and cough and higher circulating levels of neutrophil proportion,interleukin-6,low count(<190/µl)of CD8+T cells,and neutrophil/lymphocyte ratio.Thirteen patients deteriorated during hospitalization.Cox regression analysis indicated that older age and higher serum levels of interleukin-6,C-reactive protein,procalcitonin,and lactate at admission significantly predicted the progression of COVID-19.During hospitalization,circulating counts of T lymphocytes,CD4+T cells,and CD8+T cells were lower,whereas neutrophil proportion,neutrophil/lymphocyte ratio,and the circulating levels of interleukin-6,C-reactive protein,and procalcitonin were higher,in pneumonia patients than in pneumonia-free patients.CD8+lymphocyte count in pneumonia patients did not recover when discharged.Conclusions: Older age and higher levels of C-reactive protein,procalcitionin,interleukin-6,and lactate might predict COVID-19 progression.T lymphocyte,especially CD8+cell-mediated immunity is critical in recovery of COVID-19.This study may help in predicting disease progression and designing immunotherapy for COVID-19.

Association between TaqIB polymorphism of cholesteryl ester transfer protein and coronary artery disease in the Chinese population

Objective: To assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper. Methods: We searched PubMed, Embase, the Science Citation Index (SCI), the China Biological Medicine database (CBM), the China National Knowledge Infrastructure (CNKI), and the Wanfang database for relevant articles. Data were extracted, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The lit- erature search yielded 448 studies, in which 10 case-control studies including 1 694 cases and 1 456 controls matched the selection criteria. The combined B1 and B2 allele frequencies were 0.587 and 0.413, respectively. The pooled OR was 1.10 (95% CI, 0.89-1.34) for comparing the B1B1 or B1B2 carriers with B2B2 carriers, and was 1.27 (95% CI, 1.09-1.49) in the B1B1 carriers versus B2B2 or B1B2 carriers. Conclusions: In the present study, the TaqIB poly- morphism of CETP was found to be associated with CAD in the Chinese population.