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The Advanced Lung Cancer Inflammation Index (ALI) represents both the inflammatory and nutritional status of the host, but its link with mortality in asthma patients is uncertain. The purpose of this study was to look at the relationship between ALI levels and all-cause and respiratory disease mortality in asthmatic patients. We conducted our research using cohort data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The National Death Index was used to calculate mortality until December 31, 2019. The study employed multivariate logistic regression to look into the relationship between ALI levels and asthma prevalence. Weighted Kaplan-Meier and multivariate-adjusted Cox analyses were utilized for investigating the relationship between ALI levels and all-cause and respiratory disease mortality in individuals with asthma. A restricted cubic spline (RCS) analysis was used to assess their nonlinear relationship. Subgroup and sensitivity analyses were also performed to evaluate the robustness of the results that were obtained. We enrolled 40,497 people in our study, and 5,469 of them had asthma, representing a 14% prevalence. A median follow-up of 11.19 (9.38, 14.29) years revealed 109 fatalities from respiratory diseases and 724 deaths from all causes. After correcting for several covariates, there was no longer any link (P-trend = 0.2) between ALI levels and the prevalence of asthma. When compared to the lowest quartile, the highest quartile of ALI levels was substantially linked to a lower risk of mortality from respiratory diseases and all causes (all P-trend < 0.001). In the RCS regression model, the relationship between ALI level and both all-cause and respiratory disease mortality in asthmatic participants was nonlinear, with P for nonlinearity of 0.006 and 0.015, respectively. We also discovered that the probability of mortality from respiratory disease decreased progressively to a nadir at an ALI level of 109.13 and then increased as the ALI level increased. Multiple subgroup and sensitivity analyses revealed that ALI was consistently related to lower all-cause and respiratory disease mortality in asthma patients. Our findings suggest that ALI is associated with a reduced risk of all-cause and respiratory disease mortality in asthma patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The studies involving human participants were reviewed and approved by The National Center for Health Statistics (NCHS) Research Ethics Review Board. The patients/participants provided their written informed consent to participate in this study., (© 2024. The Author(s).)

Colorectal cancer (CRC) is one of the most well-known malignancies with high prevalence and poor 5-year survival. Previous studies have demonstrated that a high-fat diet (HFD) is capable of increasing the odds of developing CRC. Acrolein, an IARC group 2A carcinogen, can be formed from carbohydrates, vegetable oils, animal fats, and amino acids through the Maillard reaction during the preparation of foods. Consequently, humans are at risk of acrolein exposure through the consumption of foods rich in fat. However, whether acrolein contributes to HFD-induced CRC has not been determined. In this study, we found that acrolein induced oncogenic transformation, including faster cell cycling, proliferation, soft agar formation, sphere formation and cell migration, in NIH/3T3 cells. Using xenograft tumorigenicity assays, the acrolein-transformed NIH/3T3 clone formed tumors. In addition, cDNA microarray and bioinformatics studies by Ingenuity Pathway Analysis pointed to the fact that RAS/MAPK pathway was activated in acrolein-transformed clones that contributed to colon tumorigenesis. Furthermore, acrolein-induced DNA damages (Acr-dG adducts) were higher in CRC tumor tissues than in normal epithelial cells in CRC patients. Notably, CRC patients with higher levels of Acr-dG adducts appeared to have better prognosis. The results of this study demonstrate for the first time that acrolein is important in oncogenic transformation through activation of the RAS/MAPK signaling pathway, contributing to colon tumorigenesis.

The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides- and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.

Colorectal cancers (CRCs) are a critical health issue worldwide. Cancer stem cell (CSC) lineages are associated with tumour transformation, progression, and malignant transformation. However, how lineages are transformed and how chemoresistance is acquired by CRCs remain largely unknown. In this report, we demonstrated that the RNA-binding protein Musashi-1 enhanced the development of CD44 + colorectal CSCs and triggered the formation of anti-apoptotic stress granules (SGs). Our results indicated that CD44 + CSC lineage-specific induction of tumour malignancies was controlled by Musashi-1. In addition, Musashi-1 formed SGs when CRC cell lines were treated with 5-fluorouracil. The C-terminal domain of Musashi-1 was critical for recruitment of Musashi-1 into SGs. Intracellular Musashi-1 SGs enhanced the chemoresistance of CRCs. Analysis of clinical CRC samples indicated that Musashi-1 expression was prominent in CRC stage IIA and IIB. In summary, we demonstrated that Musashi-1, a stemness gene, is a critical modulator that promotes the development of CD44 + colorectal CSCs and also enhances CRC chemoresistance via formation of SGs. Our findings elucidated a novel mechanism of CRC chemoresistance through increased anti-apoptotic effects via Musashi-1-associated SGs.

This study was to investigate whether the time to the lowest postoperative CEA can predict cancer survival. We enrolled 155 rectal cancer patients in this retrospective and longitudinal cohort study. Deepness of response (DpR) of CEA refers to the relative change of the lowest postoperative CEA level from baseline, and time to DpR (TTDpR) refers to the time from surgery to the lowest postoperative CEA level. The median of TTDpR and DpR was 4.5 (range, 3.0-18.0) weeks and -67% (range, -99% to 114%) respectively. Patients with TTDpR 4.5 weeks. Using TTDpR as a continuous variable, the HR of DFS and OS was 1.13 (95% CI 1.06-1.22, P = 0.001) and 1.17 (95% CI 1.07-1.29, P = 0.001) respectively. On multivariate analysis, the predictive value of prolonged TTDpR remained [adjusted HRs: 1.12 (95% CI 1.03-1.21, P = 0.006) and 1.17 (95% CI 1.06-1.28, P = 0.001)]. These findings remained significant in patients with normal preoperative CEA. Our results showed prolonged TTDpR of CEA independently predicted unfavorable survival outcomes, regardless of whether preoperative CEA was elevated or not.