Objective: To investigate the relationship between serum lysophosphatidylcholine (LPC) level and the health index of the elderly. Methods: A total of 251 subjects were selected from the 2016 baseline survey of the Yongfu Longevity Cohort in Guangxi Province among whom 66, 63 and 122 were in the young and middle-aged group (≤59 years old), the young group (60-89 years old) and the longevity group (≥90 years old), respectively. Demographic data were collected and related indicators of height, weight, blood pressure and lipid metabolism were measured. The cognitive and physical functions of the elderly were assessed by the results of the simple mental state scale and the daily living activity scale to construct the health index of the elderly. The serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 were determined by liquid chromatography-tandem mass spectrometry, and the differences among different ages and health status groups were compared. The logistic regression model was used to analyze the relationship between the serum LPC level and the health index of the elderly. Results: With the increase in age, the proportion of female subjects increased, and the rate of smoking and drinking decreased. BMI, TC, TG, LDL-C, diastolic blood pressure, and the four LPCs levels decreased with the increase of age, and systolic blood pressure levels increased with the increase of age (all P values<0.05). There was no significant difference in HDL-C levels among age groups (P>0.05). With the decline of health status in the elderly, serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 showed a downward trend (all P values<0.001). After adjusting for age and gender, only LPC18∶0 was associated with the health status in old age [OR (95%CI): 0.48 (0.25-0.92)]. For every 1 standard deviation (16.87 nmol/L) increase in serum LPC18∶0 concentration, the risk of poor health status in old age decreased by 52%. Conclusion: Serum LPC18∶0 was associated with the health status in old age independent of age and sex.
Aged ; Middle Aged ; Humans ; Female ; Aged, 80 and over ; Lysophosphatidylcholines ; Risk Factors ; China ; Longevity ; Surveys and Questionnaires ; Triglycerides

Humans ; Cardiovascular Diseases ; Signal Transduction ; Lysophospholipids

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*

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

Lysophosphatidic acid (LPA) is a small phospholipid that is present in all eukaryotic tissues and blood plasma. As an extracellular signaling molecule, LPA mediates many cellular functions by binding to six known G protein-coupled receptors and activating their downstream signaling pathways. These functions indicate that LPA may play important roles in many biological processes that include organismal development, wound healing, and carcinogenesis. Recently, many studies have found that LPA has various biological effects in different kinds of bone cells. These findings suggest that LPA is a potent regulator of bone development and remodeling and holds promising application potential in bone tissue engineering. Here, we review the recent progress on the biological regulatory function of LPA in bone tissue cells.
Biological Phenomena ; Bone and Bones ; Lysophospholipids ; Receptors, Lysophosphatidic Acid

BACKGROUND: Oral cancer has a high incidence worldwide and has been closely associated with smoking, alcohol, and infection by the human papillomavirus. Metastasis is highly important for oral cancer survival. Lysophosphatidic acid (LPA) is a bioactive lipid mediator that promotes various cellular processes, including cell survival, proliferation, metastasis, and invasion. Signal transducer and activator of transcription (STATs) are transcription factors that mediate gene expression. Among the seven types of STATs in mammals, STAT3 is involved in invasion and metastasis of numerous tumors. However, little is known about the role of STAT3 in oral tumor invasion. In the present study, we hypothesized that STAT3 mediates LPA-induced oral cancer invasion. METHODS: Immunoblotting was performed to analyze LPA-induced STAT3 activation. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to assess the survival rates of YD-10B cells. STAT3 levels in LPA-treated oral tumor cells were evaluated by performing in vitro invasion assay. RESULTS: To the best of our knowledge, this is the first study to demonstrate that LPA enhances STAT3 phosphorylation in oral cancer. In addition, treatment with WP1066, a selective inhibitor of STAT3, at a concentration that does not cause severe reduction in cell viability, significantly attenuated LPA-induced YD-10B cancer cell invasion. CONCLUSION: The results suggested that LPA induces oral tumor cells with greater invasive potential via STAT3 activation. Our findings provided important insights into the mechanisms underlying mouth neoplasms.
Cell Survival ; Epithelial-Mesenchymal Transition ; Gene Expression ; Humans ; Immunoblotting ; In Vitro Techniques ; Incidence ; Lysophospholipids ; Mammals ; Mouth Neoplasms ; Neoplasm Metastasis ; Phosphorylation ; Smoke ; Smoking ; STAT3 Transcription Factor ; Survival Rate ; Transcription Factors ; Transducers

A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), compounds known to have beneficial effects in CLP, on the sepsis-induced plasma lipid changes were also examined. Among the 147 plasma lipid species from 13 lipid subgroups (fatty acid [FA], LPA, LPC, lysophosphatidylethanolamine [LPE], phosphatidic acid [PA], phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], monoacylglyceride [MG], diacylglyceride [DG], triacylglyceride [TG], sphingomyelin [SM], and ceramide [Cer]) analyzed in this study, 40 and 70 species were increased, and decreased, respectively, in the CLP mice. Treatments with LPC and LPA affected 14 species from 7 subgroups, and 25 species from 9 subgroups, respectively. These results could contribute to finding the much needed reliable biomarkers of sepsis.
Animals ; Biomarkers ; Ligation ; Lysophosphatidylcholines ; Mice* ; Peritonitis ; Phosphatidic Acids ; Phosphatidylcholines ; Phosphatidylinositols ; Plasma* ; Punctures ; Sepsis

The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor 1α and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.
Apoptosis ; Cadherins ; Carcinoma, Squamous Cell ; Cell Culture Techniques ; Cell Line ; Cell Proliferation ; Colon ; Epithelial-Mesenchymal Transition ; Gastropoda ; Humans ; Immunoblotting ; Lysophospholipids ; Mouth Neoplasms* ; Neoplasm Metastasis ; Ovarian Neoplasms ; Prostatic Neoplasms ; Stilbenes ; Transcription Factors ; Vascular Endothelial Growth Factor A

PURPOSE: We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers. MATERIALS AND METHODS: A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening. RESULTS: Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine. CONCLUSION: MALDI-TOF–based OVC LOMEs combined with triple-TOF–based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.
Biomarkers ; Colorectal Neoplasms ; Female ; Humans ; Hypoxanthine ; Lysophosphatidylcholines ; Mass Screening ; Mass Spectrometry* ; Ovarian Neoplasms* ; Pancreatic Neoplasms ; Sensitivity and Specificity

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.
Animals ; Cell Differentiation ; physiology ; Demyelinating Diseases ; chemically induced ; Lysophosphatidylcholines ; toxicity ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; metabolism ; Oligodendrocyte Precursor Cells ; cytology ; metabolism ; Oligodendroglia ; cytology ; metabolism ; Remyelination ; physiology ; Transcription Factors ; metabolism