Objective To investigate the relationship between serum platelet-activating factor (PAF) level, T cell immune function and disease activity in vitiligo patients. Methods A total of 102 patients with vitiligo treated in our hospital from July 18th, 2022 to July 26th, 2023 were enrolled as study subjects. According to VIDA score, the patients were divided into an advanced-stage group (n=54) and a stable stage group (n=49). PAF and T lymphocyte levels were compared between the two groups. Logistic regression analysis was performed to examine the relationship between PAF levels and disease activity, as well as their correlation with T cell subsets. Unconditional logistic regression modeling was employed to analyze the interaction between PAF levels and T cell subsets in disease activity. Results No significant difference was observed in CD3⁺ levels between advanced and stable stage vitiligo patients. PAF and CD8⁺ levels in advanced group were significantly higher than those in stable group, while CD4⁺ levles and CD4⁺/CD8⁺ ratios were significantly lower than those in stable group. When PAF level was 18.24 ng/L, the maximum Youden index reached 0.670, with corresponding sensitivity of 84.22% and specificity of 82.77%. The area under ROC curve AUC was 0.858. The intensity of association between PAF level and disease activity was nonlinear dose-response relationship. Among patients with VIDA score ≥1, significant differences were observed in both CD4⁺ and CD8⁺ levels across different PAF levels, and the CD4⁺/CD8⁺ ratios in vitiligo patients with different VIDA scores was significantly different. Interaction analysis revealed that after adjusting for confounding factors, the effect of PAF levels and T cell subsets on disease activity in vitiligo patients showed significant interaction in both additive model (RERI=4.674, 95%CI: 1.032~11.942; AP=0.763, 95%CI: 0.336~1.201; S=6.854, 95%CI: 1.904~16.520) and multiplicative model (OR=3.461, 95%CI: 1.365~8.713). Conclusion Serum PAF, CD4⁺, CD8⁺ and CD4⁺/CD8⁺ of vitiligo patients are closely related to disease activity, and PAF level interacts with T cell subsets (CD4⁺, CD8⁺, CD4⁺/CD8⁺) in the disease activity of vitiligo patients. PAF and T cell immune function may contribute to the occurrence and development of vitiligo, which could serve as clinical indicators of disease activity to guide timely management.
Humans ; Vitiligo/blood* ; Platelet Activating Factor/immunology* ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; T-Lymphocytes/immunology* ; Adolescent ; T-Lymphocyte Subsets/immunology*

In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and may provide more detailed information on the fertility status of the respective donor. Given the intra-individual variability of spermiogram parameters between two donations, this study sought to elucidate the biological variability of the seminal plasma metabolome over an average period of 8 weeks. Two time-shifted semen samples from 15 healthy donors were compared by a targeted metabolomics approach utilizing the Biocrates AbsoluteIDQ p180 kit. Next to intraclass correlation coefficients (ICC), which represent a measure of reliability, coefficients of variation within individuals (CVW) and coefficients of variation between individuals (CVB) were calculated for each metabolite to demonstrate its stability. Furthermore, men were divided into two cohorts, a similar sperm concentration (SSC) and a differing sperm concentration (DSC) cohort, based on the observed variance in sperm concentration between the two semen donations. The ICC was higher in the SSC compared to the DSC cohort. The levels of 18 metabolites, primarily acylcarnitines, varied between the initial and subsequent donations. After subdivision into subgroups, only ornithine and phosphatidylcholine 40:5 exhibited differential levels between the two donations in the SSC group, compared to 14 metabolites in the DSC group. CVB was higher than CVW but both differed between the metabolite subclasses. Biogenic amines were identified as the least reliable analytes over time, exhibiting the highest CVW, compared to sphingomyelins, which demonstrated the highest reliability with the lowest variation. CVB was the highest for ether-bound glycerophosphatidylcholines and the lowest for amino acids.
Humans ; Male ; Semen/metabolism* ; Metabolome ; Adult ; Sperm Count ; Carnitine/metabolism* ; Metabolomics ; Ornithine/metabolism* ; Semen Analysis ; Phosphatidylcholines/metabolism*

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Humans ; Cardiovascular Diseases ; Signal Transduction ; Lysophospholipids

Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.
Humans ; Choline/metabolism* ; Phosphatidylcholines/metabolism* ; Central Nervous System/metabolism*

Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.
Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Dental Pulp/metabolism* ; Lysophospholipids ; Osteogenesis ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Sphingosine/analogs & derivatives* ; Stem Cells

Sphingosine-1-phosphate (S1P) is the main metabolite produced in the process of phospholipid metabolism, which can promote proliferation, migration, and apoptosis of cells, and maintain the barrier function of vascular endothelium. The latest researches showed that S1P can alleviate acute lung injury (ALI) and the inflammation caused by ALI, while the dosage of S1P is still needed to be considered. Mesenchymal stem cells (MSCs) have been a emerging therapy with potential therapeutic effects on ALI because of their characteristics of self-replication and multi-directional differentiation, and their advantages in hematopoiesis, immune regulation, and tissue repair. S1P can promote differentiation of MSCs and participate in immune regulation, while MSCs can regulate the homeostasis of S1P in the body. The synergistic effect of S1P and MSC provides a new treatment method for ALI. This article reviews the production and biological function of S1P, receptor and signal pathway of S1P, the therapeutic effects of S1P on ALI, and the research advances of S1P combined with MSCs in the treatment of ALI, aiming to provide theoretical references for the development of S1P targeted drugs in the treatment of ALI and the search for new combined treatment schemes for ALI.
Acute Lung Injury ; Animals ; Lung/metabolism* ; Lysophospholipids/pharmacology* ; Mice ; Mice, Inbred C57BL ; Sphingosine/pharmacology*

OBJECTIVE: To observe the efficacy and safety of Guihuang Formula (GHF) in treating patients with type III prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis. METHODS: Sixty-six patients diagnosed with type III prostatitis with dampness-heat and blood stasis syndrome were randomly divided into the treatment group (GHF) and the control group (tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, Chinese Medicine Symptoms Score (CMSS), expressed prostatic secretions (EPS) and adverse events (AEs). RESULTS: After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups (P<0.05). The CMSS score decreased in both groups (P<0.05). The WBC count decreased and lecithin body count increased in both groups (P<0.05). GHF showed a more obvious advantage in reducing the pain discomfort and quality of life domain scores of NIH-CPSI, reducing the CMSS score, increasing the improvement rate of the WBC and lecithin body counts, compared with the control group (P<0.05). There were no significant differences in decreasing urination domain score of NIH-CPSI between two groups (P>0.05). In addition, no serious AEs were observed. CONCLUSION GHF is effective in treating type III prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs. (Registration No. ChiCTR1900026966).
Chronic Disease ; Hot Temperature ; Humans ; Lecithins ; Male ; Pain ; Prostatitis/drug therapy* ; Quality of Life ; Tamsulosin

OBJECTIVE: To compare a new thermosensitive recombinant human amelogenin (rhAm) carrier and traditional propylene glycol alginate (PGA) carrier for their characteristics, antibacterial activity, and biocompatibility with human periodontal membrane fibroblasts. METHODS: PGA-rhAm was prepared by mixing 3.3% PGA and rhAm, and CS-βGP-rhAm was prepared by mixing 2% chitosan (CS) with rhAm and then with 60% β-sodium glycerophosphate solution (βGP) as the crosslinking agent. The biophysical properties of the prepared carriers were characterized, and their antibacterial activity was assessed by observing Staphylococcus aureus growth. The biocompatibility of the carriers was evaluated in human periodontal membrane fibroblasts (hPDLFs) using CCK8 assay and scratch test, and mRNA and protein expressions of osteogenic genes of the cells incubated with the carriers were detected using RT-qPCR and Western blotting; osteogenic differentiation of the cells was detected using alkaline phosphatase staining. RESULTS: PGA-rhAm had a viscosity value of 3.262±0.055 Pa.s. CS-βGP-rhAm had a solidification capacity of 6 min at 37 ℃ with a pH value close to that of the oral cavity and a swelling rate of about 90%. CS-β GP-rhAm maintained sustained release of rhAm for over 2 weeks with a self-degradation time over 3 weeks. CS-βGPrhAm more effectively inhibited the growth of S. aureus than rhAm-loaded PGA. While PGA did not obviously affect the proliferation of hPDLFs, both CS-βGP and CS-βGP-rhAm significantly promoted the cell proliferation(P < 0.001). Scratch test showed that after rhAm loading, both CS-βGP and PGA promoted cell migration (P < 0.01). CS-βGP-rhAm significantly enhanced the mRNA expressions of RUNX2 and OCN mRNA level and the protein expressions of Ki67, RUNX2, collagen I, and β-catenin (P < 0.05); PGA-rhAm only enhanced RUNX2 (P < 0.05) and OCN (P < 0.01) mRNA expressions without significant effects on the protein expressions. Alkaline phosphatase staining results showed that CS-βGP, but not PGA, promoted osteogenic differentiation of hPDLFs. CONCLUSION CS-βGP carrier is capable of sustained release of rhAm, inhibiting the growth of S. aureus, and improving the biological activity of hPDLFs without affecting the bioactivity of rhAm after drug loading.
Alginates ; Alkaline Phosphatase ; Amelogenin ; Anti-Bacterial Agents/pharmacology* ; Cell Differentiation ; Cells, Cultured ; Chitosan/pharmacology* ; Collagen ; Core Binding Factor Alpha 1 Subunit ; Delayed-Action Preparations ; Glycerophosphates ; Humans ; Ki-67 Antigen ; Osteogenesis ; Periodontal Ligament ; RNA, Messenger ; Staphylococcus aureus ; beta Catenin

Ganoderma lingzhi is widely recognized as a medicinal basidiomycetes. Triterpene acids (TAs) are the key bioactive medicinal components of G. lingzhi. Our previous studies have shown that phospholipid acid (PA) produced by phospholipase D (PLD) plays a regulatory role in TA synthesis. In order to further elucidate the molecular mechanism how PA regulates TA synthesis in G. lingzhi, PA beads enrichment combined with LC-MS/MS technology was used to identify PA interacting proteins in G. lingzhi. A total of 19 PA interacting proteins were identified, including cytochrome P450 monooxygenase (GL22084), specific protein kinase MAPK (GL23765), catalase and cell surface hydrophobicity-associated protein. GST tagged GL22084 and GL23765 proteins were obtained through gene cloning, heterologous expression, and purification. The interactions between GL22084/GL23765 and PA were verified by GST pull down assay. The identification of PA interacting proteins provides a basis for further understanding the molecular mechanism how PLD-mediated PA signaling molecules regulates the TA synthesis in G. lingzhi. Moreover, the PA interacting proteins identified in this study can also provide clues for the research of PLD/PA signaling pathway in other species.
Chromatography, Liquid ; Ganoderma ; Phosphatidic Acids ; Tandem Mass Spectrometry