Inhibitory effect of saffron on head and neck squamous cell carcinoma via targeting of ESR1 and CCND1 by its active compound crocetin

Background:Traditional Chinese medicine is promising for managing challenging and complex disorders,including cancer,and in particular,saffron is applied in treating various cancer types.However,its potential therapeutic efficacy and active components in managing squamous cell carcinoma of the head and neck(HNSCC)remain unclear yet.Methods:Using network pharmacology approaches,active ingredients of saffron,their target genes,and HNSCC-related genes were identified.Enrichment analyses were conducted for determining molecular functions and pathways enriched by genes that overlapped between the saffron target gene set and the HNSCC gene set.Among the four known active ingredients of saffron,crocetin was found to have the strongest inhibitory impact on HNSCC,based on the findings of cell viability and migration assays.Therefore,the potential target genes of crocetin in HNSCC cells were examined using molecular docking experiments and were confirmed by qPCR.Result s:Four active ingredients of saffron and 184 of their target genes were identified.Further,a total of 34 overlapping saffron-/HNSCC-associated targets related to the four active ingredients were screened,and crocetin was chosen for further investigation because it had the strongest inhibitory effect on HNSCC cells.Molecular docking experiments indicated that ESR1 and CCND1 were the target genes of crocetin.These results were confirmed through qPCR analysis,in which crocetin was found to lower the expression of the ESR1 and CCND1 genes in AMC-HN-8 and FaDu cells.Conclusion:According to our results,crocetin is a primary active anti-cancer component of saffron that may have potential in the development of novel HNSCC-treating medications.However,more thorough molecular research is necessary for confirming these results and elucidating the anti-cancer mechanism underlying saffron.

Global research trends and hotspots in overweight/obese comorbid with depression among children and adolescents: A bibliometric analysis

BACKGROUND Overweight/obesity combined with depression among children and adolescents(ODCA)is a global concern.The bidirectional relationship between depression and overweight/obesity often leads to their comorbidity.Childhood and adolescence represent critical periods for physical and psychological development,during which the comorbidity of overweight/obesity and depression may increase the risk of adverse health outcomes.AIM To evaluate the relationship between ODCA,we conduct a bibliometric analysis to aid in formulating prevention and treatment strategies.METHODS From 2004 to 2023,articles related to ODCA were selected using the Science Citation Index Expanded from the Web of Science Core Collection.Bibliometric analysis of relevant publications,including countries/regions,institutions,authors,journals,references,and keywords,was conducted using the online bibliometric analysis platforms,CiteSpace,VOSviewer,and bibliometrix.RESULTS Between 2004 and 2023,a total of 1573 articles were published on ODCA.The United States has made leading contributions in this field,with Harvard University emerging as the leading contributor in terms of research output,and Tanofsky being the most prolific author.The J Adolescent Health has shown significant activity in this domain.Based on the results of the keyword and reference analyses,inequality,adverse childhood experiences,and comorbidities have become hot topics in ODCA.Moreover,the impact of balancedrelated behavior and exploration of the biological mechanisms,including the potential role of key adipocytokines and lipokines,as well as inflammation in ODCA,have emerged as frontier topics.CONCLUSION The trend of a significant increase in ODCA publications is expected to continue.The research findings will contribute to elucidating the pathogenic mechanisms of ODCA and its prevention and treatment.

Colonic vitamin D receptor expression is inversely associated with disease activity and jumonji domain-containing 3 in active ulcerative colitis

BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.

Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk a multicenter maternal-fetal medicine study

Background Evidence remains limited on the association between maternal ozone(O,)exposure and congenital heart defects(CHDs)in offspring,and few studies have investigated the interaction and modification of paternal smoking on this association.Methods Using a sample including pregnant women at high risk of fetal CHD(with metabolic disease,first-trimester viral infection,family history of CHD,etc.)from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021,we examined the associations between maternal O_(3)exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this association.CHD was diagnosed by fetal echocardiograms,maximum daily 8-hour average O,exposure data at a 10 km×10 km spatial resolution came from the Tracking Air Pollution in China dataset,and paternal smoking was collected using questionnaires.Logistic regression models were used to estimate adjusted odds ratios(ORs)and 95%confidence intervals(CIs).Results Among 27,834 pregnant women at high risk of fetal CHD,17.4%of fetuses were diagnosed with CHD.Each 10μg/m^(3)increase in maternal O_(3)exposure was associated with a 17%increased risk of CHD in offspring(OR=1.17,95%CI=1.14-1.20).Compared with paternal nonsmoking and maternal low O_(3)exposure,the ORs(95%CI)of CHD for smoking and low O_(3)exposure,nonsmoking and high O_(3)exposure,and smoking and high O_(3)exposure were 1.25(1.08-1.45),1.81(1.56-2.08),and 2.23(1.84-2.71),respectively.Paternal smoking cessation seemingly mitigated the increased risk of CHD.Conclusions Maternal O_(3)exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring,which calls for effective measures to decrease maternal exposure to O_(3)pollution and secondhand smoke for CHDprevention.

Greater promotion of DNRA rates and nrfA gene transcriptional activity by straw incorporation in alkaline than in acidic paddy soils

Dissimilarity nitrate reduction to ammonium(DNRA)is of significance in agriculture ecosystems as the process is beneficial to N retention in soils.However,how fertilization regimes influence DNRA rates and functional microbes in agriculture was rarely estimated.In the present study,a 2-year pot experiment was conducted in two contrasting paddy soils to evaluate the effects of straw and nitrogen addition on DNRA process and the related functional microbes,using stable isotope tracer and molecular ecology techniques.The results showed that the abundance and transcription activity of nitrite reductase encoding gene(nrfA)involved in DNRA process and DNRA rates were significantly higher in alkaline soils than in acidic soils.Straw incorporation significantly enhanced nrfA gene abundance and transcription activity,with a greater effect in alkaline soil than in acidic soil.The rates of DNRA,abundance and transcription activity of nrfA gene positively correlated to soil C/N and C/NO_(3)^(-) induced by straw application.Sequencing analysis based on nrfA gene transcript showed that Deltaproteobacteria was the most dominant group in both soil types(30.9%-67.4%),while Gammaproteobacteria,Chloroflexi,Actinobacteria were selectively enriched by straw incorporation.These results demonstrated that DNRA activity can be improved by straw return practice in paddy soils while the effect will vary among soil types due to differentiated functional microbial communities and edaphic properties.

Study on the inclusion behavior and solid inclusion complex of 5-amino-6-methyl-2-benzimidazolone with cyclodextrins

The inclusion behaviors of three native or modified CDs including p-CD,2-hydroxypropyl-β-CD（2-Hp-β-CD） and 2,6-dimethyl-β-CD（Me-β-CD） toward 5-amino-6-methyl-2-benzimidazolone（AMBI） were comparatively investigated by NMR and fluorescence titration in combination with IR spectra,X-ray diffractometry and scanning electron microphotographs.The experimental results jointly demonstrated that the phenyl ring of AMBI entered into the cavity of the CDs and located close to the narrow rims accompanied by the formation of the 1：1 inclusion complex with large stability constant in aqueous solution.The introduction of the hydroxypropyl unit to the host improved the solubility,ultimately effecting an obvious promoting in the fluorescence intensity and the stability constant

Reaction mechanism of lanthanum nitrate-doped Mo–La material during solid–liquid spray doping processing

At three critical temperatures which were obtained by thermo-gravimetry-differential thermal analysis–differential scanning calorimetry（TG/DTG/DSC）curves of lanthanum nitrate crystal, the air thermal decomposition experiments and solid–liquid spray doping simulation procedures of lanthanum nitrate crystal were carried out, and their products were analyzed by X-ray diffraction（XRD）. Meanwhile, the spray doping processing of Mo O2–50 wt% La（NO3）3composite powder was undergone with lanthanum nitrate solution as the dopant,and doped Mo O2powder was analyzed by XRD. The results demonstrate that during the traditional solid–liquid spray doping processing, lanthanum nitrate, in the form of either crystal or aqueous solution, would be converted into La（NO3）3á4H2O by the dehydration reaction, rather than be decomposed to La2O3and NO or NO2. Therefore, it is inferred that the oxynitride gas produced from the process is attributed to the decomposition of residual HNO3in lanthanum nitrate crystal. The source of HNO3is supported by the chemical composition of lanthanum nitrate crystal.