Shandong First Medical University

Krill oil, extracted from Antarctic krill, is rich in nutrients, including high concentrations of n-3 polyunsaturated fatty acids (n-3 PUFAs), phospholipids (PLs), astaxanthin, vitamins, flavonoids, and other bioactive compounds. Our previous research demonstrated that krill oil exerts anti-inflammatory, antioxidant, and metabolic regulatory effects. Given that inflammation and oxidative stress are key molecular mechanisms underlying metabolic-associated steatotic liver disease (MASLD), we investigated the protective effects and potential mechanisms of krill oil (KO) against MASLD. In this study, C57BL/6J mice were fed either a methionine- and choline-sufficient (MCS) or methionine- and choline-deficient (MCD) diet and were administered krill oil (KO) or olive oil (OO) for four weeks. Compared to control or OO intervention, KO significantly alleviated liver injury, decreased expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX4), improved oxidative stress markers, and lowered levels of the inflammatory cytokines TNF-α, IL-1β, and IL-6. Additionally, KO treatment ameliorated fibrosis such as reducing Col1a1 and Col3a1 levels and improving liver histopathology. Furthermore, KO effectively decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and p38, which belonged to mitogen-activated protein kinases (MAPK) signal pathway, and reduced the elevated levels of secreted protein acidic and rich in cysteine (SPARC) induced by MCD diet in liver. These findings are consistent with our observations in high fat diet (HFD) and streptozocin (STZ) induced type 2 diabetic mice. In vitro , KO reduced inflammation, oxidative stress, and fibrosis genes expression, as well as suppressing MAPK pathway, in human hepatic stellate cells activated by SPARC overexpression. Inflammation and oxidative stress were upregulated in macrophages which was co-cultured with SPARC overexpressed hepatic stellate cells, while KO reduced the phenotype in macrophages. Therefore, the effects of KO intervention on mitigating liver inflammation, oxidative stress, and fibrosis might associated with reduced SPARC and inhibited MAPK signaling. • KO intervention reduced liver injury and fibrosis in vivo (MCD and HFD+STZ models). • KO decreased SPARC expression and inhibited ERK/p38 phosphorylation in liver. • KO dampened inflammation and oxidative stress (lower iNOS/NOX4 and cytokines). • In SPARC-overexpressed human hepatic stellate cells, KO suppressed MAPK signaling and fibrogenic gene expression. • KO attenuated macrophage inflammatory activation induced by SPARC-overexpressing stellate cells.

Biphasic structures, which are composed of outer basal cells and inner glandular cells, are frequently indicative of salivary gland-type tumors or benign lesions, such as bronchial adenoma, within the lung. However, the occurrence of a biphasic structure in lung cancer is rarely reported and can lead to significant challenges and confusion in diagnosis, particularly in biopsy specimens. In our study, we collected eight lung epithelial tumors that presented with a distinct biphasic structure component and examined their clinicopathological characteristics. Histological examination revealed that the biphasic structure component, often intermingled with conventional squamous cell carcinoma or adenocarcinoma, was defined by basal cells encircling the glandular epithelium. Immunohistochemical analysis demonstrated a distinctive peripheral p40 staining pattern in the biphasic structure component. Genetic analysis identified driver mutations in seven out of eight patients, which are typically associated with conventional pulmonary adenocarcinomas, including EGFR L858R, EGFR 19-del, EGFR 20-ins, and KRAS mutations. The presence of biphasic structure components in these cases confirms a genuine form of lung cancer, likely representing a variant of lung adenocarcinoma. This study's findings enhance the understanding of lung cancer's morphological diversity and caution against prematurely dismissing the malignancy potential of pulmonary epithelial lesions based solely on the presence of basal cells, especially with biopsy specimens.