Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies.

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood-brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

Beyond conventional treatment: ASGR1 Leading the new era of hypercholesterolemia management.

Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with hypercholesterolemia being a major risk factor. Although various lipid-lowering therapies exist, many patients fail to achieve optimal cholesterol control, highlighting the need for novel therapeutic approaches. ASGR1 (asialoglycoprotein receptor 1), predominantly expressed on hepatocytes, has emerged as a key regulator of cholesterol metabolism and low-density lipoprotein (LDL) clearance. This receptor's ability to regulate lipid homeostasis positions it as a promising target for therapeutic intervention in hypercholesterolemia and related cardiovascular diseases. This review critically examines the biological functions and regulatory mechanisms of ASGR1 in cholesterol metabolism, with a focus on its potential as a therapeutic target for hypercholesterolemia and related cardiovascular diseases. By analyzing recent advances in ASGR1 research, this article explores its role in liver-specific pathways, the implications of ASGR1 variants in CVD risk, and the prospects for developing ASGR1-targeted therapies. This review aims to provide a foundation for future research and clinical applications in hypercholesterolemia management.

FOXN Transcription Factors: Regulation and Significant Role in Cancer.

A growing number of studies have demonstrated that cancer development is closely linked to abnormal gene expression, including alterations in the transcriptional activity of transcription factors. The Forkhead box class N (FOXN) proteins FOXN1-6 form a highly conserved class of transcription factors, which have been shown in recent years to be involved in the regulation of malignant progression in a variety of cancers. FOXNs mediate cell proliferation, cell-cycle progression, cell differentiation, metabolic homeostasis, embryonic development, DNA damage repair, tumor angiogenesis, and other critical biological processes. Therefore, transcriptional dysregulation of FOXNs can directly affect cellular physiology and promote cancer development. Numerous studies have demonstrated that the transcriptional activity of FOXNs is regulated by protein-protein interactions, microRNAs (miRNA), and posttranslational modifications (PTM). However, the mechanisms underlying the molecular regulation of FOXNs in cancer development are unclear. Here, we reviewed the molecular regulatory mechanisms of FOXNs expression and activity, their role in the malignant progression of tumors, and their value for clinical applications in cancer therapy. This review may help design experimental studies involving FOXN transcription factors, and enhance their therapeutic potential as antitumor targets.

TMEM175: A lysosomal ion channel associated with neurological diseases.

Lysosomes are acidic intracellular organelles with autophagic functions that are critical for protein degradation and mitochondrial homeostasis, while abnormalities in lysosomal physiological functions are closely associated with neurological disorders. Transmembrane protein 175 (TMEM175), an ion channel in the lysosomal membrane that is essential for maintaining lysosomal acidity, has been proven to coordinate with V-ATPase to modulate the luminal pH of the lysosome to assist the digestion of abnormal proteins and organelles. However, there is considerable controversy about the characteristics of TMEM175. In this review, we introduce the research progress on the structural, modulatory, and functional properties of TMEM175, followed by evidence of its relevance for neurological disorders. Finally, we discuss the potential value of TMEM175 as a therapeutic target in the hope of providing new directions for the treatment of neurodegenerative diseases.

Fast-Acting Black-Phosphorus-Assisted Depression Therapy with Low Toxicity.

A black phosphorus (BP)-nanosheet-based drug-delivery system containing a therapeutic drug (Fluoxetine, Flu) is synthesized. According to subsequent behavioral, biochemical, and electrophysiological analysis, BP-Flu, after irradiated with near-infrared light (808 nm), can significantly reduce the therapy time of depression. Meanwhile, the inherent biotoxicity of Flu is also alleviated.