Epigenomic analyses identify FOXM1 as a key regulator of anti-tumor immune response in esophageal adenocarcinoma.

Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in the western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify the transcription factor (TF) FOXM1 as an important epigenetic regulator of EAC. FOXM1 plays a critical role in cellular proliferation and tumor growth in EAC patient-derived organoids and cell line models. We identify ERBB2 as an upstream regulator of the expression and transcriptional activity of FOXM1. Unexpectedly, gene set enrichment analysis (GSEA) unbiased screen reveals a prominent anti-correlation between FOXM1 and immune response pathways. Indeed, syngeneic mouse models show that FOXM1 inhibits the infiltration of CD8+ T cells into the tumor microenvironment. Consistently, FOXM1 suppresses CD8+ T cell chemotaxis in vitro and antigen-dependent CD8+ T cell killing. This study characterizes FOXM1 as a significant EAC-promoting TF and elucidates its novel function in regulating anti-tumor immune response.

The effects of apoptosis inhibitor of macrophage in kidney diseases.

Kidney disease is a progressive and irreversible condition in which immunity is a contributing factor that endangers human health. It is widely acknowledged that macrophages play a significant role in developing and causing numerous kidney diseases. The increasing focus on the mechanism by which macrophages express apoptosis inhibitor of macrophages (AIM) in renal diseases has been observed. AIM is an apoptosis inhibitor that stops different things that cause apoptosis from working. This keeps AIM-bound cell types alive. Notably, the maintenance of immune cell viability regulates immunity. As our investigation progressed, we concluded that AIM has two sides when it comes to renal diseases. AIM can modulate renal phagocytosis, expedite the elimination of renal tubular cell fragments, and mitigate tissue injury. AIM can additionally exacerbate the development of renal fibrosis and kidney disease by prolonging inflammation. IgA nephropathy (IgAN) may also worsen faster if more protein is in the urine. This is because IgA and immunoglobulin M are found together and expressed. In the review, we provide a comprehensive overview of prior research and concentrate on the impacts of AIM on diverse subcategories of nephropathies. We discovered that AIM is closely associated with renal diseases by playing a positive or negative role in the onset, progression, or cure of kidney disease. AIM is thus a potentially effective therapeutic target for kidney diseases.

Excessive SOX8 reprograms energy and iron metabolism to prime hepatocellular carcinoma for ferroptosis.

Lipid peroxidation and redox imbalance are hallmarks of ferroptosis, an iron-dependent form of cell death. Growing evidence suggests that dysregulation in glycolipid metabolism and iron homeostasis substantially contribute to the development of hepatocellular carcinoma (HCC). However, there is still a lack of comprehensive understanding regarding the specific transcription factors that are capable of coordinating glycolipid and redox homeostasis to initiate the onset of ferroptosis. We discovered that overexpression of SOX8 leads to impaired mitochondria integrate, increased oxidative stress, and enhanced lipid peroxidation. These effects can be attributed to the inhibitory impact of SOX8 on de novo lipogenesis, glycolysis, the tricarboxylic acid cycle (TCA), and the pentose phosphate pathway (PPP). Additionally, upregulation of SOX8 results in reduced synthesis of NADPH, disturbance of redox homeostasis, disruption of mitochondrial structure, and impairment of the electron transport chain. Furthermore, the overexpression of SOX8 enhances the process of ferroptosis by upregulating the expression of genes associated with ferroptosis and elevating intracellular levels of ferrous ion. Importantly, the overexpressing of SOX8 has been observed to inhibit the proliferation of HCC in immunodeficient animal models. In conclusion, the findings suggest that SOX8 has the ability to alter glycolipid and iron metabolism of HCC cells, hence triggering the process of ferroptosis. The results of our study present a novel strategy for targeting ferroptosis in the therapy of HCC.

Research Progress of Pyroptosis in Renal Diseases.

Kidney diseases, particularly Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD), are identified as global public health issues affecting millions of individuals. In addition, the frequency of renal diseases in the population has increased dramatically and rapidly in recent years. Renal disorders have become a significant public health burden. The pathophysiology of renal diseases is significantly connected with renal cell death, including apoptosis, necrosis, necroptosis, ferroptosis, pyroptosis, and autophagy, as is now recognized. Unlike other forms of cell death, pyroptosis is a unique planned cell death (PCD). Scientists have proven that pyroptosis is crucial in developing various disorders, and this phenomenon is gaining increasing attention. It is considered a novel method of inflammatory cell death. Intriguingly, inflammation is among the most significant pathological characteristics of renal disease. This study investigates the effects of pyroptosis on Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy (DN), Immunoglobulin A (IgA) Nephropathy, and Lupus Nephritis (LN) to identify novel therapeutic targets for kidney diseases.

Metagenome-Assembled Genomes from Photo-Oxidized and Nonoxidized Oil-Degrading Marine Microcosms.

We performed deep metagenomic sequencing on hydrocarbon-degrading marine microcosms designed to experimentally determine the effect of photo-oxidation on oil biodegradation dynamics. Assembly, binning, and dereplication yielded 73 unique metagenome-assembled genomes (MAGs) from 6 phyla, of which 61 are predicted to be over 90% complete.