Journal of Molecular Histology最新文献

Atopic dermatitis (AD) is a chronic inflammatory skin disorder marked by immune dysregulation and oxidative stress. Current therapies, such as corticosteroids, have side effects, necessitating new treatments. This study investigates the therapeutic effects of Dendrobium officinale polysaccharides (DOP) on AD, specifically focusing on their role in modulating inflammation and mitochondrial dysfunction. An AD-like model was induced in BALB/c mice, while HaCaT keratinocytes stimulated with TNF-α/IFN-γ served as an in vitro model. In mice, DOP significantly alleviated AD symptoms, reduced inflammatory cytokines (IL-1β, IL-6) and oxidative stress markers (MDA, NO), and restored antioxidant enzyme levels (GSH, SOD, CAT). In HaCaT cells, DOP ameliorated mitochondrial dysfunction, evident by increased mitochondrial membrane potential, cellular ATP content, and normalized mitochondrial dynamics (restoring MFN1/MFN2 and reducing DRP1). Furthermore, DOP suppressed NF-κB activation both in vivo and in vitro. These findings suggest that DOP alleviates AD by reducing inflammation and oxidative stress while preserving mitochondrial homeostasis. The mechanism appears associated with NF-κB inhibition, though this link is correlational and requires further direct validation.

Several studies have shown that excessive fructose consumption increases the risk of developing metabolic syndrome (MS), which can lead to diabetes mellitus. This study aimed to evaluate the metabolic and histological abnormalities accompanying MS induced by progressive high fructose diet (HFr) in Wistar rats. Twelve Wistar rats were used, divided into two groups (n = 6) (NC and HFr). They were fed a HFr with daily administration of increasingly higher doses of fructose solutions (dose 1 = 20% from week 1 to 4, dose 2 = 25% from week 5 to 8 and dose 3 = 30% from week 9 to 12 ), during which body weight and blood glucose were measured, while an oral glucose tolerance test (OGTT) was performed, it's glucose, triglyceride, and total cholesterol concentrations were determined, and pancreatic, liver, and kidney tissues were studied at the end of the experiment. Daily administration of increasingly high doses of fructose caused body weight increase, manifested by a highly significant difference in body weight, a metabolic abnormality, differences in fasting blood glucose (hyperglycaemia), plasma concentration of glucose, glucose intolerance, and by a very significant increase of total cholesterol and triglycerides levels in blood (hyperlipidaemia) between HFr and NC groups of rats. Histopathological study showed a slight swelling of the hepatocytes and a narrowing of the blood sinusoids, as well as an inflammatory infiltration of the portal space in the hepatic section of HFr group, no morphological alterations, necrosis, or steatosis in the pancreatic and renal sections of HFr group of rats. A twelve-week HFr diet can cause some abnormalities in the liver tissue, in carbohydrate and lipid metabolism in Wistar rats without damaging their pancreas and kidneys, which may be explained by the fact that metabolic abnormalities can precede histological lesions.

Emerging evidence suggests a crucial role of MARCH8, a membrane-associated RING-E3 ubiquitin ligase, in cancer progression by regulating the turnover of cancer-related proteins. Our previous research identified potential MARCH8 targets using an RNAi-coupled proteomics approach, revealing that MARCH8 mediates the proteasomal degradation of E-cadherin and β2m, contributing to Esophageal Squamous Cell Carcinoma (ESCC) progression. Additionally, EpCAM emerged as a key target, and this study aims to investigate how MARCH8 regulates EpCAM stability and its implications in tumor migration. Herein, Co-immunoprecipitation (Co-IP) and Western Blotting (WB) demonstrated that MARCH8 directly interacts with EpCAM and regulates its turnover by ubiquitination and proteasomal degradation. Further, MARCH8-EpCAM co-localization was observed in ESCC cells using Immunofluorescence (IF). Additionally, Immunohistochemistry (IHC) analysis in ESCC tissues revealed a significant inverse correlation between MARCH8 and EpCAM expression (r = -0.6730, p < 0.0001). Interestingly, EpCAM showed a context-dependent expression in esophageal tissues. Adjacent non-malignant esophageal squamous epithelium showed no detectable EpCAM staining, superficial tumor regions displayed membranous EpCAM expression, whereas tumor cells at the deeper invasive front exhibited markedly reduced or lost EpCAM expression. Consistently, scratch assay coupled with IF and IHC analysis further demonstrated reduced EpCAM expression in migrating ESCC cells. Overexpression studies further revealed an inverse relationship between MARCH8 and EpCAM in migration, invasion, and β-catenin signaling, as shown by invasion/migration assays and WB analysis. Collectively, these findings establish EpCAM as a novel target of MARCH8. Given that loss of EpCAM is associated with migratory phenotypes and that MARCH8 promotes ESCC progression, MARCH8-driven EpCAM degradation may contribute to enhanced tumor cell migration and disease progression.

Aging is a long-term and complex process characterized by cellular changes, including cell cycle arrest, increased production of the senescence-associated secretory phenotype (SASP), and nuclear membrane disintegration. To accelerate the aging process, various animal models are made using chemical inducers, such as D-galactose (D-Gal). D-Gal has been extensively applied to induce aging in experimental animals; however, its effects on the gastrointestinal system, particularly the colon, remain underexplored. Observation of molecular aging markers will provide a valuable approach to assess these cellular changes. This study aimed to observe the expression of genes related to cell cycle arrest (p53 and Cdkn1a), SASP production (Il-6 and Il-1β), nuclear membrane disintegration (Lmnb1), as well as histological inflammation process in the colon of D-Gal-induced aging rat models. Twelve-week-old male Sprague-Dawley rats (n = 12) were divided into the control and D-Gal (100 mg/kg/day for 6 weeks) groups. The expression levels of aging-related genes (p53, Cdkn1a, Il-6, Il-1β, and Lmnb1) were assessed by reverse-transcription quantitative polymerase chain reaction. The D-Gal group exhibited inflammatory cell infiltration. Il-1β immunohistochemical score along with Il-1β expression was significantly elevated in D-Gal group (p < 0.01), suggesting SASP activation and pro-inflammatory signaling. No statistically significant differences were observed in the expression levels of p53, Il-6, Cdkn1a, or Lmnb1 expression. Molecular and histological results demonstrated that D-Gal administration induces colonic inflammation, characterized by increased Il-1β expression, which subsequently promotes potential cellular senescence.