Connection between inflammation and carcinogenesis in gastrointestinal tract: Focus on TGF-β signaling

Inflammation is a primary defense process against various extracellular stimuli,such as viruses,pathogens,foods,and environmental pollutants.When cells respond to stimuli for short periods of time,it results in acute or physiological inflammation.However,if the stimulation is sustained for longer time or a pathological state occurs,it is known as chronic or pathological inflammation.Several studies have shown that tumorigenesis in the gastrointestinal (GI) tract is closely associated with chronic inflammation,for which abnormal cellular alterations that accompany chronic inflammation such as oxidative stresses,gene mutations,epigenetic changes,and inflammatory cytokines,are shared with carcinogenic processes,which forms a critical cross-link between chronic inflammation and carcinogenesis.Transforming growth factor (TGF)-β is a multi-potent cytokine that plays an important role in regulation of cell growth,apoptosis and differentiation.Most importantly,TGF-β is a strong anti-inflammatory cytokine that regulates the development of effector cells.TGF-β has a suppressive effect on carcinogenesis under normal conditions by inhibiting abnormal cell growth,but on the other hand,many GI cancers originate from uncontrolled cell growth and differentiation by genetic loss of TGF-β signaling molecules or perturbation of TGF-β adaptors.Once a tumor has developed,TGF-β exerts a promoting effect on the tumor itself and stromal cells to enhance cell growth,alter the responsiveness of tumor cells to stimulate invasion and metastasis,and inhibited immune surveillance.Therefore,novel development of therapeutic agents to inhibit TGF-β-induced progression of tumor and to retain its growth inhibitory activities,in addition to anti-inflammatory actions,could be useful in oncology.In this review,we discuss the role of TGF-β in inflammation and carcinogenesis of the GI tract related to abnormal TGF-β signaling.

Vitamin A supplementation downregulates ADH1C and ALDH1A1 mRNA expression in weaned beef calves

Our previous studies demonstrated that oral vitamin A supplementation during late-stage pregnancy and the neonatal stage enhances birth weight,growth performance,and mRNA expression related to muscle and preadipocyte development in beef cattle.The alcohol dehydrogenase 1C(ADH1C)c.-64T>C genotype also correlated with vitamin A concentration in beef production.This study aimed to investigate the effects of vitamin A supplementation on the muscle development and vitamin A metabolism in weaned beef calves with different ADH1C genotypes.Twenty male calves(90 d of age;initial BW:89.03 kg[SD 8.60])were stratified according to ADH1C genotype and vitamin A treatment(duration:3 months)and randomly assigned to 4 groups with a 22 factorial arrangement.Vitamin A treatments included the following:control(10,000 IU/kg of as-fed,a.TT type;b.TC type);treatment(40,000 IU/kg of as-fed,c.TT type;and d.TC type).Parameters including BW,FI,blood,longissimus dorsi muscle,and liver status during the experimental period were analyzed using the generalized linear model(GLM)procedure and Tukey's test by SAS 9.4 program.Serum vitamin A was significantly increased(P<0.05)in the vitamin A treatment group at 4 and 6 months of age.TT type calves showed higher serum vitamin A concentration(P<0.05)than the TC type calves.Serum triglyceride and non-esterified fatty acid(NEFA)levels increased(P<0.05)in the treatment group compared with the control at 6 months of age.However,BW,ADG and FI showed no differences between the groups.In addition,mRNA expression in longissimus dorsi muscle revealed upregulation of paired box 7(PAX7)(P<0.05)after the vitamin A treatment period based on biopsy results.Both ADH1C and aldehyde dehydrogenase(ALDH)1A1 mRNA expression was downregulated(P<0.01)by vitamin A supplementation.The TC type of ADH1C showed higher mRNA expression than the TT type.However,no effect was observed on adipogenic mRNA expression(preadipocyte factor-1[PREF-1],peroxisome proliferator-activated receptor gamma[PPARg],fatty acid binding protein 4[FABP4])in all groups.Our findings suggest that weaned calves treated with vitamin A may promote the storage of satellite cells by elevating PAX7 gene expression in the muscle.The TC type calves may show increased capacity for vitamin A metabolism,which can be used in genetically customizing feed management to maximize beef production in the calves.