A potentially fatal ailment, abdominal aortic aneurysms (AAAs) frequently result in death by dissection or rupture. AAA is caused by a histopathologic anomaly that includes smooth muscle cell loss, media degeneration, inflammatory cell infiltration, and elastic fiber damage in the aorta wall. Nevertheless, it is still unknown how AAAs form. Improved knowledge of how AAA develops and progresses might lead to the development of innovative, less intrusive treatment approaches for those suffering from this debilitating illness. Functional foods have a range of protective impacts, such as antioxidant, anti‐inflammatory, antifibrotic, anticarcinogenic, and cardiovascular protective impacts, as shown by numerous human and animal research. Pretreatment with nutraceuticals can suppress the growth of AAA and pro‐inflammatory markers. The use of nutraceuticals to treat ischemic‐reperfusion cardiac cells has been shown to protect against ischemia–reperfusion damage through a diversity of mechanisms. This information was most recently reported. Thus, by inhibiting apoptosis, oxidative damage, c‐Jun N‐terminal kinase pathway, and inflammation, we investigated the impact of nutraceuticals on experimental‐induced AAA in the current review.

Aberrant SUMOylation has been associated with cancer, neurodegenerative diseases, and infections, but its exact role in glioblastoma (GBM) remains unknown. This study aimed to uncover this link and identify novel biomarkers for GBM treatment. NPC2, SPI1, and LRRC25 were identified as prognostic biomarkers for GBM outcomes. MR analysis showed that NPC2 and LRRC25 increased GBM risk, while SPI1 had a protective effect. A nomogram effectively predicted GBM prognosis. These biomarkers were enriched in pathways such as allograft rejection, inflammatory response, and IL6-JAK-STAT3 signaling. Significant immune differences were found between GBM and normal groups, with NPC2 correlating with M2 macrophages and activated NK cells, and SPI1 with HAVCR2. These biomarkers were expressed in actively propagating macrophages, macrophages, and dendritic cells, and were consistently up regulated in GBM datasets. These findings suggest that NPC2, SPI1, and LRRC25 are SUMOylation-related biomarkers for GBM, offering potential novel therapeutic targets.

HOPX acts as a tumor suppressor in certain cancers, but the function of HOPX, as well as its mechanism of action in hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, using in vitro and in vivo animal models, the effect of HOPX on the development of HCC was explored. In our study, the HOPX expression at both protein and mRNA level were found to be downregulated in HCC cells and tumor tissues. Restoration of HOPX expression was found to inhibit HCC cell invasion and migration capabilities, but produced no effect on growth. Moreover, HOPX prevented metastasis in an HCC cell metastatic mouse model. Further investigations showed that HOPX could suppress HCC cell epithelial-to-mesenchymal transition (EMT) by inhibiting SNAIL, an EMT transcription factor that is required for the metastasis-inhibition activity of HOPX to proceed. Our study identified HOPX as a suppressor of the development of HCC, which implies that HOPX suppresses HCC cells invasion and migration by inhibiting SNAIL.

The full text of this preprint has been withdrawn by the authors while they make corrections to the work. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

BackgroundGliomas are the most prevalent and aggressive primary brain tumors. Aging significantly influences glioma incidence and progression, yet the molecular mechanisms linking aging-related pathways to tumor aggressiveness remain poorly understood. Here, we aimed to decipher aging-related molecular mechanisms regulating tumor aggressiveness in gliomas.MethodsWe performed comprehensive aging-targeted transcriptomic analyses using TCGA-glioma patient dataset. Differential gene and protein expression, functional annotation and pathway enrichment, gene set enrichment, network construction, CRSISPR-based functional dependency, transcription factor prediction, correlation, clinical association and survival analyses were conducted to identify, develop and validate endoplasmic reticulum (ER) stress-driven unfolded protein response (UPR) as key aging-related molecular mechanism driving tumor aggressiveness in gliomas. Notably, we validated our findings in multiple independent GEO datasets.ResultsWe identified ER stress and UPR as key aging-related mechanism behind tumor aggressiveness in gliomas, and developed a six gene “ER Stress and UPR-driven Aging-related Tumor Aggressiveness in Glioma” (ESURATAG) gene signature, comprising DERL2, RPN2, SEC13, SEC61A1, SEC61B, and STT3A. Notably, glioma cell proliferation critically depends on ESURATAG-GS, which is preferentially regulated by MYC and is associated with disease and cell cycle progression, inflammation, and poor clinical outcomes in glioma patients, simultaneously aligning with aging and tumor aggressiveness signatures. Validated in multiple GEO datasets, high ESURATAG expression is linked to disease onset, advanced disease state, and reduced overall and progression-free survival in glioma patients as well as in patients with major subtypes of gliomas, including oligodendrogliomas, astrocytomas and gliobalstomas.DiscussionESURATAG-GS serves as a critical MYC-regulated adaptive mechanism that fuels aging-related tumor aggressiveness via ER stress-driven UPR in gliomas, presenting novel prognostic markers and therapeutic targets for elderly glioma patients.

Backgrounds. Glioma stands as one of the most formidable brain tumor types, with patient outcomes remaining bleak even in the face of advancements in treatment modalities. FBXW4, a constituent of the F-box and WD repeat domain-containing protein family, is recognized for its participation in diverse cellular activities, including those related to tumor dynamics. Yet, the therapeutic relevance and specific role of FBXW4 in the context of glioma are not well defined. This study aims to elucidate the functional dynamics and significance of FBXW4 in glioma cases. Methods. This research undertook a comprehensive analysis of FBXW4’s expression patterns and clinical relevance in glioma by harnessing data from the TCGA and GTEx databases. Results. The investigation revealed a distinct downregulation of FBXW4 in glioma tissues compared to normal brain counterparts, with a pronounced correlation between FBXW4 levels and disease severity. Intriguingly, FBXW4 expression inversely related to WHO tumor grades, with the most advanced grade IV gliomas exhibiting the lowest FBXW4 levels, whereas grade II tumors demonstrated the highest. Cases presenting with IDH1/2 mutations or 1p/19q codeletions were also associated with elevated FBXW4 levels. Furthermore, diminished FBXW4 expression aligned with an increased risk of mortality. Conclusions. The findings suggest that FBXW4 holds promise as a prognostic marker and a potential therapeutic avenue in glioma management. Nonetheless, future research is imperative to decode the intricate signaling pathways involving FBXW4 and to understand its broader clinical ramifications in glioma treatment paradigms.

Adoptive cell therapy (ACT) has been demonstrated to be one of the most promising cancer immunotherapy strategies due to its active antitumor capabilities in vivo. Engineering T cells to overexpress chimeric antigen receptors (CARs), for example, has shown potent efficacy in the therapy of some hematologic malignancies. However, the efficacy of chimeric antigen receptor T cell (CAR-T) therapy against solid tumors is still limited due to the immunosuppressive tumor microenvironment (TME) of solid tumors, difficulty in infiltrating tumor sites, lack of tumor-specific antigens, antigen escape, and severe side effects. In contrast, macrophages expressing CARs (CAR-macrophages) have emerged as another promising candidate in immunotherapy, particularly for solid tumors. Now at its nascent stage (with only one clinical trial progressing), CAR-macrophage still shows inspiring potential advantages over CAR-T in treating solid tumors, including more abundant antitumor mechanisms and better infiltration into tumors. In this review, we discuss the relationships and differences between CAR-T and CAR-macrophage therapies in terms of their CAR structures, antitumor mechanisms, challenges faced in treating solid tumors, and insights gleaned from clinical trials and practice for solid tumors. We especially highlight the potential advantages of CAR-macrophage therapy over CAR-T for solid tumors. Understanding these relationships and differences provides new insight into possible optimization strategies of both these two therapies in solid tumor treatment.

PDF file - 165K, FOXO1 plays an important role in GOLPH3 mediated-proliferation

PDF file - 95K, IHC analysis of GOLPH3 expression in normal breast tissues and breast cancer tissues with different degrees of differentiation

<p>PDF file - 59K, IHC analysis of GOLPH3 and Ki-67 expression in breast cancer tissues</p>

miR-452 overexpression represses Wnt/β-catenin signaling.

PDF file - 65K, Kaplan-Meier overall survival curves and log-rank test of overall survival

PDF file - 45K, GOLPH3 expression is upregulated in breast cancer

miR-452 directly targets Bmi-1, LEF1 and TCF4.

<p>PDF file - 159K, IHC analysis of GOLPH3, Ki67 and cyclin D1 expression and H&E staining in tumor xenograft tissues</p>

<p>PDF file - 59K, IHC analysis of GOLPH3 and Ki-67 expression in breast cancer tissues</p>

<p>PDF file - 211K, GOLPH3 specially affects FOXO1 transactivity through modulation of FOXO1 sub-cellular localization</p>

<p>PDF file - 159K, IHC analysis of GOLPH3, Ki67 and cyclin D1 expression and H&E staining in tumor xenograft tissues</p>

<p>PDF file - 211K, GOLPH3 specially affects FOXO1 transactivity through modulation of FOXO1 sub-cellular localization</p>