Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.

Environmental exposure to perchlorate,nitrate,and thiocyanate in relation to chronic kidney disease in the general US population,NHANES 2005-2016

Background:Few studies have explored the impact of perchlorate,nitrate,and thiocyanate(PNT)on kidney function.This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease(CKD)among the general population in the United States.Methods:This analysis included data from 13,373 adults(≥20 years)from the National Health and Nutrition Examination Survey 2005 to 2016.We used multivariable linear and logistic regression,to explore the associations of urinary PNT with kidney function.Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes.Results:After traditional creatinine adjustment,perchlorate(P-traditional)was positively associated with estimated glomerular filtration rate(eGFR)(adjustedβ:2.75;95%confidence interval[CI]:2.25 to 3.26;P<0.001),and negatively associated with urinary albumin-to-creatinine ratio(ACR)(adjustedβ:-0.05;95%CI:-0.07 to-0.02;P=0.001)in adjusted models.After both traditional and covariate-adjusted creatinine adjustment,urinary nitrate and thiocyanate were positively associated with eGFR(all P values<0.05),and negatively associated with ACR(all P values<0.05);higher nitrate or thiocyanate was associated with a lower risk of CKD(all P values<0.001).Moreover,there were L-shaped non-linear associations between nitrate,thiocyanate,and outcomes.In the adjusted models,for quartiles of PNT,statistically significant dose-response associations were observed in most relationships.Most results were consistent in the stratified and sensitivity analyses.Conclusions:Exposures to PNT might be associated with kidney function,indicating a potential beneficial effect of environmental PNT exposure(especially nitrate and thiocyanate)on the human kidney.