Vitamin D receptor (VDR) signaling plays a crucial role in hair follicle biology and represents a promising therapeutic target for various forms of alopecia. This review comprehensively examines the molecular mechanisms of VDR signaling in hair follicle development, cycling, and pathology. We discuss key molecular mechanisms of VDR‐dependent gene regulation through chromatin remodeling, transcriptional regulation, and recruitment of coregulatory complexes, which collectively regulate hair follicle homeostasis. Recent advances in understanding VDR genetic polymorphisms and their impact on treatment responses have provided new insights into personalized therapeutic approaches. The review explores current therapeutic strategies, from conventional vitamin D supplementation to emerging targeted delivery systems and combination therapies. We also analyze the challenges and limitations in current research, including the need for improved delivery systems and reliable biomarkers for treatment response prediction. The integration of molecular insights with clinical applications suggests promising directions for developing more effective, personalized treatments for various forms of alopecia. This comprehensive analysis underscores the significance of VDR‐targeted approaches in the future management of hair disorders and highlights the importance of continued research in this field.

Lupus nephritis (LN), a renal manifestation of systemic lupus erythematosus, results from immune‐mediated kidney injury. The present study investigated how complement component 5a (C5a) and its receptor (C5aR1) regulate phosphatase and tensin homolog (PTEN) expression and the phosphoinositide 3‐kinase (PI3K)/AKT pathway during LN development. Using MRL/lpr mice as an LN model, we examined the expression of C5a, C5aR1, PTEN, and related proteins through Western blot, quantitative real‐time PCR, and immunohistochemistry. Treatment with a C5aR1 antagonist (C5aR1A) was administered to assess its effects on renal function and molecular parameters. Elevated expression of C5a and C5aR1 was detected in MRL/lpr mice, accompanied by reduced PTEN levels and enhanced PI3K/AKT signaling activity. Treatment with the C5aR1 antagonist (C5aR1A) restored PTEN expression, suppressed AKT phosphorylation, and improved renal function, reflected by lower serum creatinine and blood urea nitrogen concentrations. These findings suggest that the C5a/C5aR1 axis contributes to LN progression by regulating PTEN and the PI3K/AKT signaling pathway, offering potential therapeutic insights for LN treatment.

Depression involves multifaceted molecular pathways, with astrocyte pyroptosis emerging as a critical contributor to neuroinflammation. This study reveals that geniposide, a natural compound, alleviates depressive‐like behaviors in chronic unpredictable mild stress mice by targeting a long non‐coding RNA (lncRNA)‐mediated signaling axis. Bioinformatics analysis identified Six3os1 as a key lncRNA sponging miR‐511‐3p, thereby upregulating COL9A3 and suppressing the MAPK/NLRP3 pathway. Behavioral tests (sucrose preference, tail suspension, and Morris water maze) demonstrated that geniposide (100 mg/kg) reversed CUMS‐induced depressive behaviors. Histological and molecular analyses confirmed geniposide's ability to restore hippocampal integrity, reduce astrocyte pyroptosis, and downregulate pyroptosis markers (ASC, cleaved Casp‐1, GSDMD‐N, and IL‐1β). Dual‐luciferase and RNA pull‐down assays validated the Six3os1/miR‐511‐3p/COL9A3 interaction, whereas Western blotting showed geniposide inhibited MAPK phosphorylation (p‐p38, p‐ERK1/2) and NLRP3 activation. Overexpression of Six3os1 or silencing of miR‐511‐3p mimicked geniposide's effects, whereas COL9A3 knockdown exacerbated pyroptosis. These findings establish a novel ceRNA mechanism wherein geniposide modulates astrocyte survival via Six3os1‐dependent regulation of miR‐511‐3p and MAPK/NLRP3 signaling, offering therapeutic insights for depression.

Paraptosis is a non‐apoptotic form of programmed cell death, distinct from classical apoptosis in morphology and mechanism. It has been implicated in tumor resistance and immune microenvironment remodeling, but its role in breast cancer (BC) remains unclear. We classified patients into two subtypes based on the expression of paraptosis‐related genes. Then, we systematically analyzed the prognosis and tumor microenvironment (TME) associated with these subtypes. In addition, we developed a risk score, named the paraptosis‐related risk score (PRRS). We comprehensively analyzed the correlation of paraptosis with BC prognosis, TME, immune score, and drug sensitivity. Then, we performed in vitro experiments to verify the effect of PI4KB on BC. The PRRS can effectively predict the prognosis and immunity of BC. Low PRRS was associated with a favorable prognosis, characterized by reduced tumor purity and enhanced immune cell infiltration. In addition, PRRS can help identify patients who are suitable for specific drug therapies. Finally, we found that PI4KB was highly expressed in BC. Knockdown of PI4KB expression significantly suppressed BC cell proliferation and migration. Our study establishes a robust framework for BC subtype classification and prognostic prediction, providing novel guidance for personalized therapeutic strategies.

This study investigates the molecular mechanisms of early stent placement intervention in mitigating neurovascular unit damage and cerebral microcirculatory disorder (CMD) associated with severe internal carotid artery stenosis (ICAS). By utilizing a rat model of severe ICAS, early stent placement was found to improve cerebral blood flow, restore blood–brain barrier (BBB) integrity, and alleviate cognitive deficits by downregulating intercellular adhesion molecule 1 (ICAM1) expression. Transcriptomic analysis highlighted ICAM1's role in neurovascular repair by modulating inflammatory pathways and BBB‐associated tight junction proteins. In vitro experiments supported that ICAM1 knockdown enhanced BBB function by reducing inflammatory cytokines and promoting cell proliferation and migration. However, rescue experiments demonstrated that ICAM1 overexpression impeded the therapeutic effect of stent placement by exacerbating CMD and BBB disruption through upregulation of matrix metalloproteinase‐9 (MMP‐9) and inflammatory cytokines. These findings suggest that targeting ICAM1‐related pathways could optimize stent treatment strategies, emphasizing the importance of ICAM1 regulation in reducing the risk of watershed infarction and improving therapeutic outcomes in ICAS management.

Hypoxic pulmonary arterial hypertension (PAH) is a severe cardiovascular condition involving vascular remodeling and inflammation. Jagged2 (Jag2) has been implicated in various pathologies but its role in PAH remains unclear. We integrated bioinformatics analysis of transcriptomic data with in vitro and in vivo experiments to investigate Jag2's function in hypoxic PAH. We focused on primary rat pulmonary artery smooth muscle cells (PASMCs) for cellular responses and a rat model for hemodynamic changes. Jag2 was upregulated under hypoxic conditions, promoting PASMC proliferation and migration and inhibiting apoptosis through NADPH oxidase 2 (NOX2)/reactive oxygen species (ROS) signaling. Inhibition of Jag2 ameliorated hemodynamic changes and vascular remodeling in the PAH rat model. Jag2 activation of NOX2/ROS signaling is a critical driver of vascular inflammation and remodeling in hypoxic PAH, suggesting the Jag2/NOX2 axis as a therapeutic target.

This study aimed to examine the regulatory role of leukocyte immunoglobulin‐like receptor B2 (LILRB2) in macrophage extracellular trap (MET) formation in foam macrophages in atherosclerosis (AS). Three datasets were subjected to bioinformatics analysis to identify differentially expressed genes (DEGs). Atherosclerotic lesions from patients with AS were subjected to hematoxylin and eosin and oil red O staining. The levels of lipid regulation‐related proteins and inflammatory factors were measured in the lesions. MET formation was induced in oxidized low‐density lipoprotein‐treated foam macrophages with tumor necrosis factor‐alpha (TNF‐α). LILRB2 knockdown cells were established to evaluate the role of LILRB2 in MET formation. In a rat AS model, the levels of PI3K/AKT signaling pathway‐related molecules and METs were measured in groups classified based on LILRB2 expression. LILRB2 was a key DEG in foam macrophages in AS. The atherosclerotic tissues exhibited increased levels of lipid accumulation and METs and dysregulation of lipid‐related and inflammatory factors. Treatment with TNF‐α promoted MET formation and LILRB2 expression. Y‐P 740 treatment mitigated the LILRB2 knockdown‐induced suppression of PI3K/AKT signaling and MET formation. LILRB2 mediated AS pathogenesis by promoting MET formation in foam macrophages via the PI3K/AKT pathway. Targeting LILRB2 and its associated signaling pathway was a potential novel therapeutic strategy for AS.

Colorectal cancer (CRC) progression involves liquid–liquid phase separation (LLPS), but its prognostic significance remains unexplored. Using The Cancer Genome Atlas transcriptomic data, we developed an LLPS‐based risk model that outperformed traditional clustering methods. High‐risk patients exhibited worse outcomes, correlating with higher tumor mutational burden and reduced natural killer/T‐cell infiltration, yet increased predicted response to immune checkpoint blockade. Drug sensitivity analysis suggested therapeutic efficacy of Entinostat and 5‐fluorouracil in this subgroup. Five pivotal genes (ASXL1, DDX21, HNRNPA1L2, TACC3, and TRIM28) were identified as LLPS‐driven regulators of CRC progression, mechanistically linking phase separation to epigenetic dysregulation, aberrant RNA splicing, and metabolic reprogramming. Our study provides the first LLPS‐associated prognostic framework for CRC, offering both a risk stratification tool and actionable therapeutic insights. The findings highlight LLPS as a critical molecular organizer in CRC pathogenesis and a potential target for precision oncology approaches.

Ovarian cancer remains a major threat to women's health due to difficulties in early detection and limited treatment options. In this study, we investigate the role of FTO (fat mass and obesity‐associated protein), a key demethylase involved in N6‐methyladenosine (m6A) RNA modification, in the progression of ovarian cancer. Bioinformatics analysis of public datasets, along with validation in clinical samples, revealed that FTO expression was significantly lower in ovarian cancer tissues compared to normal controls. Functional assays demonstrated that FTO downregulation was associated with enhanced proliferation, migration, and invasion of ovarian cancer cells, which coincide with elevated global m6A methylation levels. Conversely, overexpression of FTO in vitro and in vivo significantly inhibited these tumorigenic phenotypes and suppressed tumor growth in a mouse xenograft model. Mechanistic studies demonstrated that FTO is localized in both the nucleus and cytoplasm and that its tumor‐suppressive effects are mediated, at least in part, through modulation of Ki67 expression. Together, these findings highlight FTO as a critical negative regulator of ovarian cancer progression and underscore the potential of targeting m6A methylation pathways as a therapeutic target. This research provides novel insights into the epitranscriptomic regulation of ovarian cancer and lays the groundwork for FTO‐based therapeutic development.