Recent progress in aptamer-based microfluidics for the detection of circulating tumor cells and extracellular vesicles

Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circulating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

Research progress on natural products against hepatocellular carcinoma

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

Causal effect of education on type 2 diabetes:A network Mendelian randomization study

BACKGROUND The causality between education and type 2 diabetes(T2DM)remains unclear.AIM To identify the causality between education and T2DM and the potential metabolic risk factors[coronary heart disease(CHD),total cholesterol,lowdensity lipoprotein,triglycerides(TG),body mass index(BMI),waist circumference(WC),waist-to-hip ratio(WHR),fasting insulin,fasting glucose,and glycated hemoglobin]from summarized genome-wide association study(GWAS)data used a network Mendelian randomization(MR).METHODS Two-sample MR and network MR were performed to obtain the causality between education-T2DM,education-mediator,and mediator-T2DM.Summary statistics from the Social Science Genetic Association Consortium(discovery data)and Neale Lab consortium(replication data)were used for education and DIAGRAMplusMetabochip for T2DM.RESULTS The odds ratio for T2DM was 0.392(95%CI:0.263-0.583)per standard deviation increase(3.6 years)in education by the inverse variance weighted method,without heterogeneity or horizontal pleiotropy.Education was genetically associated with CHD,TG,BMI,WC,and WHR in the discovery phase,yet only the results for CHD,BMI,and WC were replicated in the replication data.Moreover,BMI was genetically associated with T2DM.CONCLUSION Short education was found to be associated with an increased T2DM risk.BMI might serve as a potential mediator between them.

Isorhapontigenin protects against doxorubicin-induced cardiotoxicity via increasing YAP1 expression

As an effective anticancer drug, the clinical limitation of doxorubicin(Dox) is the time-and dose-dependent cardiotoxicity. Yes-associated protein 1(YAP1) interacts with transcription factor TEA domain 1(TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced in vivo and in vitro cardiotoxic model. Ectopic expression of Yap1 significantly blocked Dox-induced cardiomyocytes apoptosis in TEAD1 dependent manner. Isorhapontigenin(Isor) is a new derivative of stilbene and responsible for a wide range of biological processes. Here, we found that Isor effectively relieved Doxinduced cardiomyocytes apoptosis in a dose-dependent manner in vitro. Administration with Isor(30 mg/kg/day, intraperitoneally, 3 weeks) significantly protected against Dox-induced cardiotoxicity in mice. Interestingly, Isor increased Dox-caused repression in YAP1 and the expression of its target genes in vivo and in vitro. Knockout or inhibition of Yap1 blocked the protective effects of Isor on Dox-induced cardiotoxicity. In conclusion, YAP1 may be a novel target for Dox-induced cardiotoxicity and Isor might be a new compound to fight against Dox-induced cardiotoxicity by increasing YAP1 expression.

Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress

Ulcerative colitis(UC)is a chronic and recurrent inflammatory bowel disease(IBD)that has become a major gastroenterologic problem during recent decades.Numerous complicating factors are involved in UC development such as oxidative stress,inflammation,and microbiota disorder.These factors exacerbate damage to the intestinal mucosal barrier.Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products.However,there have been few studies on the treatment of UC using S.platensis aqueous extracts(SP),and the underlying mechanism of action of SP against UC has not yet been elucidated.Herein,we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier.Dextran sulfate sodium(DSS)was used to establish a normal human colonic epithelial cell(NCM460)injury model and UC animal model.The mitochondrial membrane potential assay 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and staining with Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model.Moreover,hematoxylin and eosin(H&E)staining,transmission electron microscopy(TEM),enzyme-linked immunosorbent assay(ELISA),quantitative real-time polymerase chain reaction(qPCR),western blot,and 16S ribosomal DNA(rDNA)sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice.In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury.SP also significantly reduced the excessive generation of intracellular reactive oxygen species(ROS)and prevented mitochondrial membrane potential reduction after DSS challenge.In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group.Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins(TJs)post-SP treatment.SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon.Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction,inhibition of DSS-induced ROS production,and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.