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Diabetic nephropathy (DN) is a primary diabetic complication ascribed to the pathological changes in renal microvessels. This study investigated the nuclear factor erythroid 2‐related factor 2 (Nrf2)/Kelch ECH associating protein (Keap1)/antioxidant response element (ARE) signaling pathway impact of chitooligosaccharides (COS) with a certain degree of polymerization (DP) on DN mouse models and high glucose‐damaged human kidney 2 (HK‐2) cells. The findings indicated that COS effectively reduced the renal function indexes (uric acid [UA], urinary albumin excretion rate [UAER], urine albumin‐to‐creatinine ratio [UACR], blood urea nitrogen [BUN], and creatinine [Cre]) of DN mice. It increased (p <.05) the superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and catalase (CAT) antioxidant enzyme activity in the serum and kidneys, and decreased (p <.05) the malondialdehyde (MDA) content. The mechanistic investigation showed that COS significantly increased (p <.05) Nrf2 and downstream target gene (GCLM, GCLC, HO‐1, and NQO‐1) expression, and substantially decreased (p <.05) Keap1 expression. The protein level was consistent with the messenger RNA (mRNA) level in in vitro and in vivo models. The docking data indicated that COS and Keap1 protein binding included six hydrogen bond formation processes (Gly364, Arg415, Arg483, His436, Ser431, and Arg380). The COS intervention mechanism may be related to the Nrf2/Keap1/ARE antioxidant pathway. Therefore, it provides a scientific basis for COS application in developing special medical food for DN patients. [ABSTRACT FROM AUTHOR]

• The effect of COS on the microecology of NAFLD patients were evaluated. • Treated with COS, the microbial beta diversity of NAFLD patients was shifted. • The target microorganisms of COS were determined. • The differential metabolites of COS were related to the changes of microorganisms. Chitobiose (OC)and chitotriose (TOC)were used to simulate the in vitro fermentation of feces samples from nonalcoholic fatty liver disease (NAFLD) patients to evaluate their effects on gut microorganisms and metabolites. The results indicated that OC and TOC shifted the gut microbial community of NAFLD patients to that of healthy volunteers. Specifically, OC and TOC increased the relative abundance of Fusobacteria, while reducing Actinobacteria and the ratio of Firmicutes to Bacteroidetes. OC's targeted bacteria were Fusobacterium , Clostridium sensu stricto 13 and Parabacteroides , while TOC's targeted bacteria were Clostridium sensu stricto 1 , Enterococcus. The content of total short-chain fatty acids, propionic acid and butyric acid in the OC and TOC groups increased significantly, which was closely related to the increase in the abundance of the targeted flora. Although the non-targeted metabolites of OC and TOC had a high degree of similarity in the positive ion mode and a large difference in the negative ion mode. The up-regulated metabolites of the OC and TOC groups include bile acids (7-ketodeoxycholic acid, docosahexaenoic acid ethyl ester, deoxycholic acid, cholic acid), amino acids (succinyl proline, cys-tyr, L-β-leucine), antibiotics (fortimicin FU-10, kanoamine), and down-regulated metabolites include xanthine, hypoxanthine, L-glutamic acid, acetophenone, etc. The biomarker metabolites of OC and TOC may reveal the probiotic effect on gut microecological health on the biosynthesis of amino acids, butyric and bile acid metabolism pathways. The results can be helpful for the further development of COS as a functional food. [ABSTRACT FROM AUTHOR]

• High-degree-polymerized COS were obtained by enzyme-membrane coupling reactor. • COS treatment of C33A cells induced ROS production and decreased the MMP. • COS treatment induced cell apoptosis and regulated apoptotic-related proteins. • COS treatment increased the levels of autophagy markers. Gynecological cancers are the most commonly diagnosed forms of cancer among the female population. Chitooligosaccharides (COS)—hydrolysis products from chitosan—display high bioavailability, high water solubility, and low molecular weight properties. Here, we investigated the influence of COS on 11 gynecological tumor cell types, and subsequently elucidated molecular mechanisms through which the observed inhibition occurred. Initially, we used a controllable enzyme-membrane coupling reactor system to obtain COS with a high degree of polymerization; the yield of high-degree-polymerized COS (DP 5–12) obtained with this reactor system accounted for ∼75% yields (w/w). Using these COS materials, cell line assays showed that COS elicited the most significant anti-tumor activity against C33A cells, with anti-tumor mechanisms related to oxidative stress, as well as activation of intrinsic mitochondrial apoptosis and autophagic signaling. Thus, we provide experimental evidence to demonstrate how the enzyme-membrane coupling reactor system can generate COS that exert bioactivity against gynecological cancers. [ABSTRACT FROM AUTHOR]

This study investigated the intervention effects of chitooligosaccharides (COS) on retinol metabolism and included comparisons of the retinol level, retinol binding protein 4 (RBP4) content, key genes, and protein expression between mice on a COS‐enriched diet and a normal diet. The results showed that COS markedly decreased the retinol and RBP4 concentrations in the serum and liver. Furthermore, COS suppressed the mRNA and protein expression of RBP4, cellular retinol binding protein 1 (CRBP1), lecithin: retinol acyltransferase (LRAT) and cytochrome P45026A1 (CYP26A1). In addition, COS inhibited the mRNA expression of stimulated by retinoic acid 6 (STRA6). However, the protein expression of STRA6 was not significantly decreased. Thus, COS reduced the retinol concentration in the serum and disrupted the metabolism of retinol. The intervention mechanism of COS on retinol metabolism may be attributed to the modulation of RBP4, CRBP1, LRAT, STRA6, and CYP26A1 expression at the mRNA and protein levels. Practical applications: Chitooligosaccharides (COS), known to be the degradation products of chitosan, have been found to induce pinkeye in industrial workers who participate in the manufacturing of COS. Meanwhile, 5% population with COS dietary supplement also have similar phenomenon. The aim of this study is to explore the possible mechanism underlay of this potential risk. The results of this study showed that high exposure to COS during manufacture influences retinol metabolism and leads to a decrease in retinol content, ultimately causing pinkeye. These findings provide new evidence for understanding COS‐induced retinol metabolism alteration and drawing attention toward the prevention of potential risk in high‐exposure populations. [ABSTRACT FROM AUTHOR]

Oral administration of chitooligosaccharides (COS) has been reported to alleviate colitis in mice. However, the mechanism of action of COS with specific polymerization degree on gut inflammation and metabolism remains unclear. This study aimed to investigate the effects of chitobiose (COS2), chitotetraose (COS4), and chitohexaose (COS6) on colitis, and to elucidate their underlying mechanisms. COS2, COS4, and COS6 were able to significantly alleviate colonic injury and inflammation levels. COS6 has the best anti-inflammatory effect. Furthermore, COS6 could down-regulate the level of indoleamine-2,3-dioxygenase1 (IDO1) and restore the levels of indole, indoleacetic-3-acid (IAA), and indole-3-carbaldehyde (I3A) in the cecum of chronic colitis mice (p < 0.05), thereby regulating tryptophan metabolism. In the aromatic hydrocarbon receptor-IL-22 (AHR-IL-22) pathway, although there were differences between chronic colitis and acute colitis mice, COS intervention could restore the AHR-IL-22 pathway to normal, promote the expression of MUC2, and repair the intestinal mucosal barrier. In conclusion, the results of this study suggested that COS had a good inhibitory effect on IDO1 under inflammation and the changes of AHR and IL-22 levels at different stages of disease development. This provides new insights into the potential use of COS as a functional food for improving intestinal inflammation and metabolism. [Display omitted] • Dosage and polymerization of chitooligosaccharides affect its activity in colitis. • Colonic aryl hydrocarbon receptor during acute colitis and remission periods varied. • Chitohexaose exhibited the most potent anti-inflammatory effect. • Chitohexaose significantly enhanced the production of intestinal indole-3-carbaldehyde. • The correlation between chitooligosaccharides dosage and polymerization-gut metabolism-colitis was established. [ABSTRACT FROM AUTHOR]

AZD9291 can prolong the survival of patients with non-small cell lung cancer. Unfortunately, resistance to AZD9291 is inevitable and hinders effectiveness. Studies showed the combination of Cyclosporin A (CsA) and AZD9291 could increase the efficacy of AZD9291, but the delivery efficiency of free drugs was limited. A chitooligosaccharide (COS) -based nanoparticle with enhanced delivery efficiency and endocytosis was constructed in this study. The results showed that this pH/redox cascade responsive nanoparticles improved therapeutic effect. The system is small and the surface charge changed from negative to positive according to the weakly acidic tumor microenvironment. After endocytosis, the nanoparticles decomposed and released AZD9291 and CsA in redox-rich cytoplasm. Experiments in vitro and in vivo proved that the nanoparticles overcame the biological barrier and significantly enhanced the anti-tumor effect of AZD9291. The novel multifunctional nanoparticle provides a way to overcome the drug resistance and the possibility of clinical application. [Display omitted] [ABSTRACT FROM AUTHOR]