Aldolase A (A-2) (ALD), Kelch-like-ECH associated protein-1 (Keap-1), and Forkhead box O4 (FoxO4) are key regulatory proteins, which have been proven to be involved in tumor development. However, the clinicopathological significance of ALD, Keap-1, and FoxO4 expressions in colorectal (colon) carcinoma (CRC) is not clearly known. We sought to explore the clinicopathological significance of ALD, Keap-1, and FoxO4 in CRC to provide evidences for potential monitoring index of CRC. Cases of 199 CRC patients were analyzed retrospectively. Evaluation of ALD, cAMP response element-binding protein-2, cyclo-oxygenase 2, FoxO4, Keap-1, and p53 expressions in CRC patients was accomplished with immunohistochemical technique. The patients were divided into negative and positive groups in accordance with immunohistochemical result. We compared the clinicopathological characteristics of the patients in the 2 groups, coupled with analysis of the relationship between 6 aforesaid proteins and clinicopathological characteristics. Herein, we confirmed the association of tumor location with the expression of ALD, Keap-1, and FoxO4. Also, tumor differentiation was observed to associate significantly with the expression of Keap-1, FoxO4, and Cox-2. The data also revealed that there was a correlation between smoking and expression of ALD, Keap-1, FoxO4, p53, and Cox-2. Nevertheless, insignificant difference was observed when clinicopathological characteristics were compared with cAMP response element-binding protein-2 expression. These findings suggest that ALD, Keap-1, and FoxO4 reinvolved in CRC development, and thus may be considered as potential monitoring protein for CRC.

Post-translational modification (PTM) encompasses diverse modifications, including phosphorylation, methylation, ubiquitin-like modifications (UBLs), and so on, which profoundly influence cellular functions. UFMylation is a recently identified ubiquitin-like modification, which is mediated by the Ubiquitin-like Ubiquitin Fold Modifier 1 (UFM1) conjugation system. The UFM1 conjugation system comprises UFM1, Ubiquitin-like protein activating enzyme 5 (UBA5), UFM1-conjugating enzyme 1 (UFC1), UFM1-specific ligase 1 (UFL1), UFM1-specific protease 1 (UFSP1), UFM1-specific protease 2 (UFSP2), UFM1-binding protein 1 (UFBP1), and CDK5 regulatory subunit-associated protein 3 (CDK5RAP3). Accumulating research has demonstrated that the UFM1 conjugation system regulates various cellular stress responses, including endoplasmic reticulum (ER) stress, protein trafficking, DNA damage repair, and autophagy. Additionally, abnormal stress adaptations of the UFM1 conjugation system contribute to the pathophysiological complications of inflammatory diseases and cancer, underscoring its significance as a key regulatory node in human health and disease. Therefore, this review provides a comprehensive exploration of the structural characteristics of UFM1 conjugation system members and the mechanistic roles of UFMylation by UFM1 conjugation system-mediated diseases related to cellular stress responses, which will not only facilitate the identification of novel diagnostic and prognostic indicators but also enable the identification of specific therapeutic targets for UFM1 conjugation system-related diseases.

Cadmium (Cd) is a ubiquitous heavy metal environmental toxicant, and exposure poses a persistent public health concern due to its bioaccumulative properties. However, the impact of maternal Cd exposure on mammary gland function during lactation remains insufficiently understood. In this study, we investigated the effects of Cd exposure during pregnancy and lactation on mammary gland development, hormonal homeostasis, and lactational performance using a drinking water exposure model. Pregnant 7-week-old ICR mice were randomly assigned into Control and Cd groups. The Control group received standard drinking water, while the Cd group was administered water supplemented with Cd (12 mg/L). Results demonstrated that maternal Cd exposure markedly reduced maternal and offspring weight, respectively. Histological analysis revealed that Cd exposure resulted in decreased numbers of mammary alveoli and widened interstitial spaces, indicating impaired mammary development. In addition, Cd exposure markedly compromised lactational performance, as reflected by reduced milk yield and decreased levels of milk protein, fat, and lactose across multiple lactation stages. Integrated metabolomic and transcriptomic analyses further revealed substantial alterations in hormonal profiles and metabolic pathways associated with mammary gland function. Notably, Cd accumulation was detected in mammary tissue and milk, accompanied by transcriptional changes in genes involved in milk synthesis and lipid metabolism. In conclusion, these findings indicated that maternal Cd exposure during pregnancy and lactation is associated with structural and functional alterations of the mammary gland, leading to reduced lactational performance and impaired offspring growth. The findings contribute to a better understanding of the risks posed by environmental Cd exposure, emphasizing the need for effective public health strategies to mitigate its impact on maternal and infant health.

Irritable bowel syndrome (IBS) is a multifactorial functional intestinal disorder whose pathogenesis involves intestinal microbiota imbalance, mucosal barrier impairment, immune–inflammatory responses, and dysregulation of the gut–brain axis. Lactobacillus reuteri has been shown to modulate the gut microbiota, produce antimicrobial metabolites, strengthen the intestinal mucosal barrier, suppress inflammatory responses, and participate in gut–brain axis regulation, thereby potentially contributing to the maintenance of intestinal homeostasis and the alleviation of IBS-related symptoms. These findings indicate that L. reuteri holds potential therapeutic value in the prevention and treatment of IBS. However, the majority of supporting evidence derives from animal experiments, in vitro studies, or indirect sources, and its precise mechanisms of action and clinical efficacy warrant further investigation.