Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic acids(miRNAs)as potential biomarkers for HCC diagnosis.RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p.The miRNA profiles also revealed the tumor stages of HCC patients.High expression of miR-455-5p and miR-30c-5p,which significantly correlated with better overall survival in tumor tissues,could also be detected in blood exosomes.Two pairs of miRNAs(miR-584-5p/miR-106-3p and miR-628-3p/miR-941)showed a 94.1%sensitivity and 68.4%specificity to differentiate HCC patients from non-HCC patients.The specificity of the combination was substantially influenced by alcohol consumption habits.CONCLUSION This study suggested that blood exosomal miRNAs can be used as new noninvasive diagnostic tools for HCC.However,their accuracy could be affected by tumor stage and alcohol consumption habits.

Downregulation of Na^＋/Ca^2＋ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats

Background：Calcium regulatory proteins-L-type Ca^2＋ channels （LTCCs）,ryanodine receptor 2 （RyR2）,and Na^＋/Ca^2＋ exchanger isoform 1 （NCX1） have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury （I/RI）.Both sevofturane postconditioning （SevoPoC） and delayed remote ischemic preconditioning （DRIPC） have been shown to protect the heart against I/RI.In this study,we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model.Methods：After 30-min balanced perfusion,isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion.Totally 40 isolated hearts were randomly assigned to four groups （n =10/group）：time control group,I/RI group,SevoPoC group,and DRIPC group.The effect of SevoPoC （3% v/v） and DRIPC were observed.Myocardial infarct size （IS）,cardiac troponin I level,and heart function were measured.The protein and messenger RNA levels of LTCCs,RyR2,and NCX1 were determined.Results：Both SevoPoC and DRIPC improved the recovery of myocardial function,and reduced cardiac troponin Ⅰ release after I/RI.The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group （16.50% ± 4.54% in the SevoPoC group [P =0.0006],and 22.34% ± 4.02% in the DRIPC group [P =0.0007] vs.35.00% ± 5.24% in the I/RI group,respectively）.SevoPoC,but not DRIPC significantly inhibited the activity of NCX 1 （0.59 ＋ 0.09 in the I/RI group vs.0.32 ± 0.16 in the SevoPoC group,P =0.006;vs.0.57 ± 0.14 in the DRIPC group,P =0.072）.No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC.In addition,subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin Ⅰ level and the protein expression ofNCX1 （r =0.505,P =0.023）.Conclusion：SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.

The molecular biology of pancreatic adenocarcinoma:translational challenges and clinical perspectives

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence.Furthermore,it is usually diagnosed at an advanced stage with a very dismal prognosis.Due to the high heterogeneity,metabolic reprogramming,and dense stromal environment associated with pancreatic cancer,patients benefit little from current conventional therapy.Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification,thus expanding clinical therapeutic options.In this review,we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression.We further discuss potential biomarkers for pancreatic cancer diagnosis,prediction,and surveillance based on novel liquid biopsies.We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models.Finally,we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.

Transcriptome analysis and functional gene identification reveals potential mechanisms of heat stress response of Lactiplantibacillus plantarum CGMCC8198

Lactiplantibacillus plantarum is an important probiotic bacterium and extensively applied to functional food.Its survival is strongly affected by the heat-shock process during manufacture.Acclimation is thought to be able to enhance bacteria resistance to heat stress.In this study,the results of transcriptomics and bioinformatics analysis showed that alcohol dehydrogenase adhE-like,phosphoribose-ATP pyrophosphatase hisE,flavodoxin ykuN,and dihydropterin aldolase folB might be related with heat resistance of L.plantarum CGMCC8198.Furthermore,after these genes were expressed in Escherichia coli,survival rate,hydrophobicity and membrane integrity of the recombinant bacteria under high temperature were also significantly improved.Besides,by screening the strains after multiple rounds of acclimation,a strain(XH)with better heat tolerance was obtained,and the results of qRT-PCR showed that these four genes,especially hisE,were upregulated in the acclimated strain when it was treated with high temperature.These findings indicated that adhE-like and some other potential genes could improve the heat resistance of lactic acid bacteria,and might be used as indicators for screening of heat-tolerant probiotics strains.