The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full-thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.

UNASSIGNED: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.
UNASSIGNED: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK-8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.
UNASSIGNED: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.
UNASSIGNED: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.

UNASSIGNED: Red blood cell distribution width-to-albumin ratio (RAR) is a combined new indicator reflecting immunology and has been reported to predict the prognosis of inflammation-related diseases and brain diseases. However, the association and predictive value of RAR in the prognosis of patients with autoimmune encephalitis (AE) has not been reported.
UNASSIGNED: This was a retrospective cohort study, and data were collected from the Henan Provincial People\'s Hospital. RAR was categorized according to quartile. The prognosis was assessed using the modified Rankin Scale (mRS), and an mRS score of ≥3 was defined as a poor prognosis. The logistical regression model was used to explore the association between RAR and the prognosis, with results reported as odds ratio (OR) and 95% confidence interval (CI). The predictive value of RAR was evaluated by calculating the area under the receiving operating curve (AUC), sensitivity, specificity, and accuracy.
UNASSIGNED: A total of 175 eligible patients were included for analysis, and 51 patients were identified as having poor prognosis. After adjusting age, cancer, other diseases, histological subtype, antiepileptic therapy, anti-tumor treatment, ICU treatment, and length of stay, RAR in the highest quartile (Q4) was found to be significantly associated with the high odds of poor prognosis (OR = 5.63, 95%CI: 1.98-16.02) compared to RAR in the lowest quartile (Q1). In addition, RAR was identified as a predictor for the prognosis of AE patients (AUC = 0.660, 95%CI: 0.574-0.746).
UNASSIGNED: This study found the close association and predictive value of RAR for the prognosis of AE patients, indicating that RAR might help clinicians identify high-risk populations.

BACKGROUND: This study aims to investigate the potential correlation between baseline red cell distribution width (RDW) to albumin ratio (RAR) levels and treatment failure in peritoneal dialysis-associated peritonitis (PDAP) patients.
METHODS: A retrospective single-center study was conducted on 286 PDAP patients. Logistic regression and generalized estimation equation (GEE) analyses were employed to assess the relationship between RAR and treatment failure.
RESULTS: RAR emerged as a robust predictor of treatment failure in PDAP patients. Elevated RAR levels were associated with an increased risk of treatment failure, exhibiting a linear relationship. Even after adjusting for demographic and clinical variables, this association remained statistically significant. ROC analysis revealed that RAR outperformed RDW and albumin individually in predicting PDAP prognosis.
CONCLUSIONS: This study highlights RAR as a superior prognostic marker for treatment failure in PDAP patients, offering new insights into risk assessment and management strategies for this challenging condition.

OBJECTIVE: The aim of this study was to ascertain whether red cell distribution width-to-albumin ratio (RAR) is associated with survival in hepatitis B virus (HBV)-associated decompensated cirrhosis (DC) patients.
METHODS: A cohort of 167 patients with confirmed HBV-DC was enrolled in our study. Demographic characteristics and laboratory data were obtained. The main endpoint was mortality at 30 days. The receiver operating characteristic curve and multivariable regression analysis were used to assess the power of RAR for predicting prognosis.
RESULTS: Mortality at 30 days was 11.4% (19/167). The RAR levels were higher in the nonsurvivors than the survivors, and elevated RAR levels were clearly associated with poor prognosis. Moreover, the predictive powers of RAR and Model for End-Stage Liver Disease score were not obviously different.
CONCLUSIONS: Our data indicate that RAR is a novel potential prognostic biomarker of mortality in HBV-DC.

UNASSIGNED: Red blood cell distribution width (RDW) to albumin ratio (RAR) is associated with poor prognosis in diabetic comorbidities and cancer. However, the association between RAR and prognosis in patients with sepsis remains unclear, which was investigated in this study.
UNASSIGNED: We conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC) IV version 2.0 database. The primary outcome of this study was 28-day mortality. Secondary outcomes included 90-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Multivariate regression analysis and subgroup analysis were performed to investigate the association between RAR and prognosis in patients with sepsis.
UNASSIGNED: A total of 14,639 participants were included in this study. The mean age of the participants was 65.2 ± 16.3 years and the mean RAR was 5.5 ± 1.9 % /g/dl. For 28-day mortality, after adjusting for covariates, HRs [95% confidence intervals (CIs)] for tertiles 2 (4.4-5.8) and 3 (RAR > 5.8) were 1.33 (1.20, 1.46) and 1.98 (1.79, 2.19), respectively. Similar results were observed for 90-day mortality and in-hospital mortality. According to Kaplan-Meier curve analysis, the higher RAR group had higher 28-day mortality and 90-day mortality.
UNASSIGNED: Our study shows that RAR is significantly associated with poor clinical prognosis in sepsis. The higher the RAR, the higher the 28-day, 90-day, and in-hospital mortality.

Male fertility depends on the regulatory balance between germ cell self-renewal and differentiation, and the spatial and temporal patterns of this balance must be maintained throughout the life cycle. Retinoic acid and its receptors are important factors in spermatogenesis. Spermatogonia cells can self-proliferate and differentiate and have unique meiotic capabilities; they halve their genetic material and produce monomorphic sperm to pass genetic material to the next generation. A number of studies have found that the spermatogenesis process is halted in animals with vitamin A deficiency and that most germ cells are degraded, but they tend to recover after treatment with RA or vitamin A. This literature review discusses our understanding of how RA regulates sperm cell differentiation and meiosis and also reviews the functional information and details of RA.

Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells.
The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM.
The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis.
ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling.
ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.

Evoking tumor cellular senescence, an irreversible status of cell growth quiescence, has been recently proposed as a potential strategy to improve the efficacy of cancer treatment. In the current study, all-trans retinal, the precursor of all-trans retinoic acid, was conjugated to dextran via hydrazone bond to generate amphiphilic dextran-retinal (DR) conjugates, which self-assembled into pH-sensitive DR micelles. Our results showed that DR micelles moderately inhibited MCF-7 breast cancer cell growth through inducing p21-associated cellular senescence, which relied on retinoic acid receptors (RARs) and was accompanied by significant G0/G1 cell cycle arrest. Moreover, DR micelles were capable of encapsulating doxorubicin (DOX) to generate DOX-loaded DD micelles, facilitating the uptake and release of DOX in cancer cells. Compared with free DOX, DD micelles more effectively suppressed tumor growth and prolonged survival time of mouse xenograft model through inducing tumor apoptosis and cellular senescence. However, blocking cellular senescence diminished DD-caused apoptosis in MCF-7 cells by 40-50%. Therefore, pH-sensitive DR micelles not only served as a potent platform for DOX delivery, but also enhanced the anti-tumor effect of DOX by inducing tumor cellular senescence. These data reveal a great potential of evoking tumor senescence with retinal-conjugated micelles for boosting breast cancer chemotherapy.

Inflammatory bowel disease (IBD) is characterized by excessive innate immune cell activation, which is responsible for tissue damage and induction of adaptive immune responses. All-trans retinoic acid (ATRA), the ligand of retinoic acid receptors (RAR), has been previously shown to regulate adaptive immune responses and restore Th17/Treg balance, while its role in regulation of innate immune cell function such as macrophages remains to be elucidated. The study was performed to explore the effect of ATRA on regulation of innate immune responses during dextran sulfate sodium (DSS) induced murine colitis. The mice with DSS colitis were administered with vehicle, ATRA, or LE135. Colitis was evaluated by clinical symptoms, tissue myeloperoxidase (MPO) activity, and the expressions of CD68 and nuclear factor (NF) κB p65, and tumor necrosis factor (TNF) level in inflamed colon. RAW 264.7 cells were pretreated with vehicle, ATRA, or LE135, followed by LPS challenge in vitro. ATRA administration ameliorates DSS-induced colitis evidenced with decreased TNF level and CD68 expression, while LE135 leads to exacerbation of colitis. ATRA treatment in vitro dampens LPS induced NF-κB activation and TNF production of RAW 264.7 cells. Together, our data show a crucial role of ATRA in the progress of acute colitis through inhibiting NF-κB activation, and suggest that ATRA represents a novel therapeutic approach for the management of IBD.