Bioenergetic alteration in gastrointestinal cancers:The good,the bad and the ugly

Cancer cells exhibit metabolic reprogramming and bioenergetic alteration,utilizing glucose fermentation for energy production,known as the Warburg effect.However,there are a lack of comprehensive reviews summarizing the metabolic reprogramming,bioenergetic alteration,and their oncogenetic links in gastrointestinal(GI)cancers.Furthermore,the efficacy and treatment potential of emerging anticancer drugs targeting these alterations in GI cancers require further evaluation.This review highlights the interplay between aerobic glycolysis,the tricarboxylic acid(TCA)cycle,and oxidative phosphorylation(OXPHOS)in cancer cells,as well as hypotheses on the molecular mechanisms that trigger this alteration.The role of hypoxia-inducible transcription factors,tumor suppressors,and the oncogenetic link between hypoxia-related enzymes,bioenergetic changes,and GI cancer are also discussed.This review emphasizes the potential of targeting bioenergetic regulators for anti-cancer therapy,particularly for GI cancers.Emphasizing the potential of targeting bioenergetic regulators for GI cancer therapy,the review categorizes these regulators into aerobic glycolysis/lactate biosynthesis/transportation and TCA cycle/coupled OXPHOS.We also detail various anti-cancer drugs and strategies that have produced pre-clinical and/or clinical evidence in treating GI cancers,as well as the challenges posed by these drugs.Here we highlight that understanding dysregulated cancer cell bioenergetics is critical for effective treatments,although the diverse metabolic patterns present challenges for targeted therapies.Further research is needed to comprehend the specific mechanisms of inhibiting bioenergetic enzymes,address side effects,and leverage high-throughput multi-omics and spatial omics to gain insights into cancer cell heterogeneity for targeted bioenergetic therapies.

Usefulness of fecal lactoferrin in predicting and monitoring the clinical severity of infectious diarrhea

AIM:To explore the value of fecal lactoferrin in predicting and monitoring the clinical severity of infectious diarrhea.METHODS:Patients with acute infectious diarrhea ranging from 3 mo to 10 years in age were enrolled,and one to three stool samples from each subject were collected.Certain parameters,including white blood cells /differential count,C-reactive protein,fecal mucus,fecal pus cells,duration of fever,vomiting,diarrhea and severity(indicated by Clark and Vesikari scores),were recorded and analyzed.Fecal lactoferrin was determined by enzyme-linked immunosorbent assay and compared in different pathogen and disease activity.Generalized estimating equations(GEE) were also used for analysis.RESULTS:Data included 226 evaluations for 117 individuals across three different time points.Fecal lactoferrin was higher in patients with Salmonella(11.17 μg/g ± 2.73 μg/g) or Campylobacter(10.32 μg/g ± 2.94 μg/g) infections and lower in patients with rotavirus(2.82 μg/g ± 1.27 μg/g) or norovirus(3.16 μg/g ± 1.18 μg/g) infections.Concentrations of fecal lactoferrin were significantly elevated in patients with severe(11.32 μg/g ± 3.29 μg/g) or moderate(3.77 μg/g ± 2.08 μg/g) disease activity compared with subjects with mild(1.51 μg/g ± 1.36 μg/g) disease activity(P < 0.05).GEE analysis suggests that this marker could be used to monitor the severity and course of gastrointestinal infections and may provide information for disease management.CONCLUSION:Fecal lactoferrin increased during bacterial infection and with greater disease severity and may be a good marker for predicting and monitoring intestinal inflammation in children with infectious diarrhea.