Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

Metabolomic changes in children with autism

BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book chapter.METHODS A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January 2024.Inclusion criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.

Comparative associations of non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease with risk of incident chronic kidney disease:a cohort study

Background:We examined the comparative associations between non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)definitions with risk of developing chronic kidney disease(CKD)and abnormal albuminuria.Methods:We conducted a cohort study of 214,145 Korean adults with normal kidney function at baseline who underwent liver ultrasonography.Participants were further subdivided into no steatotic liver disease(no-SLD),NAFLD-only,MASLD-only,both NAFLD and MASLD,and SLD not categorized as NAFLD or MASLD groups.Cox proportional hazards models were used to analyze the risk of incident CKD and albuminuria.Results:Compared with either the no-NAFLD or no-MASLD groups,the NAFLD and MASLD groups were associated with a higher risk of incident CKD(NAFLD:adjusted hazard ratio(HR),1.18[95%CI,1.01-1.38];MASLD:adjusted HR,1.21[95%CI,1.04-1.39]).Among the five subgroups,both NAFLD and MASLD group had the strongest association with risk of incident CKD(adjusted HR,1.21[95%CI,1.04-1.42]).The MASLD-only group had the strongest association with incident abnormal albuminuria,with an adjusted HR comparable to that of the both NAFLD and MASLD group(adjusted HR 1.96[95%CI,1.44-2.67]for the MASLD-only,and adjusted HR 1.98[95%CI,1.58-2.49]for the both NAFLD and MASLD group versus the no-SLD group).The NAFLD-only group was not independently associated with risk of CKD or abnormal albuminuria.Conclusions:These findings suggest that MASLD definition identifies individuals at high risk of developing incident CKD or abnormal albuminuria better than NAFLD definition.

Water-dispersible nano-pollutions reshape microbial metabolism in type-specific manners:A metabolic and bacteriological investigation in Escherichia coli

Incomplete separation and recycling of nanoparticles are causing undesirable nanopollution and thus raising great concerns with regard to nanosafety.Since microorganisms are important regulator of physiological processes in many organisms,the interaction between nanopollution and microbial metabolomics and the resultant impact on the host’s health are important but unclear.To investigate how typical nanopollution perturbs microbial growth and metabolism,Escherichia coli(E.coli)in vitro was treated with six water-dispersible nanomaterials(nanoplastic,nanosilver,nano-TiO 2,nano-ZnO,semiconductor quantum dots(QDs),carbon dots(CDs))at human-/environment-relevant concentration levels.The nanomaterials exhibited type-specific toxic effects on E.coli growth.Global metabolite profiling was used to characterize metabolic disruption patterns in the model microorganism exposed to different nanopollutants.The percentage of significant metabolites(p<0.05,VIP>1)accounted for 6%–38%of the total 293 identified metabolites in each of the nanomaterial-contaminated bacterial groups.Metabolic results also exhibited significant differences between different nanopollutants and dose levels,revealing type-specific and untypical concentration-dependent metabolic responses.Key metabolites responsive to nanopollution exposures were mainly involved in amino acid and purine metabolisms,where 5,4,and 7 significant metabolic features were included in arginine and proline metabolism,phenylalanine metabolism,and purine metabolism,respectively.In conclusion,this study horizontally compared and demonstrated how typical nanopollution perturbs microbial growth and metabolomics in a type-specific manner,which broadens our understanding of the ecotoxicity of nanopollutants on microorganisms.