Prostaglandins & other lipid mediators最新文献

Periodontitis is featured as the periodontium’s pathologic destruction caused by the host’s overwhelmed inflammation. Omentin-1 has been reported to be aberrantly downregulated in patients with periodontitis, but the specific regulation of Omentin-1 during the pathogenesis of periodontitis remains unclear. In this study, human periodontal ligament stem cells (hPDLSCs) were stimulated by lipopolysaccharide (LPS) from Porphyromonas gingivalis to establish an in vitro inflammatory periodontitis model. hPDLSCs were treated with recombinant human Omentin-1 (250, 500 and 750 ng/mL) for 3 h before LPS stimulation. Results revealed that Omentin-1 significantly inhibited LPS-induced inflammation in hPDLSCs through reducing the production of proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6) and downregulating the expression of Cox2 and iNOS. Meanwhile, Omentin-1 significantly enhanced alkaline phosphatase (ALP) activity and Alizarin red-stained area, accompanied by increasing expression osteogenic markers BMP2, OCN and Runx2, confirming that Omentin-1 restores osteogenic differentiation in LPS-induced hPDLSCs. In addition, the conditioned medium (CM) from LPS-induced hPDLSCs was harvested to culture macrophages, which resulted in macrophage polarization towards M1, while CM from Omentin-1-treated hPDLSCs reduced M1 macrophages polarization and elevated M2 polarization. Furthermore, Omentin-1 also inhibited LPS-triggered endoplasmic reticulum (ER) stress in hPDLSCs, and additional treatment of the ER stress activator tunicamycin (TM) partially reversed the functions of Omentin-1 on inflammation, osteogenic differentiation and macrophages polarization. In summary, Omentin-1 exerted a protective role against periodontitis through inhibiting inflammation and enhancing osteogenic differentiation of hPDLSCs, providing a novelty treatment option for periodontitis.

We reported that lysophosphatidic acid (LPA) is present at 0.8 μM in mixed human saliva (MS). In this study, we examined the distribution, origin, and enzymatic generation pathways of LPA in MS. LPA was distributed in the medium and cell pellet fraction; a true level of soluble LPA in MS was about 150 nM. The soluble LPA was assumed to be generated by ecto-type lysophospholipase D on exfoliated cells in MS from LPC that originated mainly from the major salivary gland saliva. Our results with the albumin-back extraction procedures suggest that a significant pool of LPA is kept in the outer layer of the plasma membranes of detached oral mucosal cells. Such pool of LPA may contribute to wound healing in upper digestive organs including oral cavity. We obtained evidence that the choline-producing activity in MS was mainly due to Ca²⁺-activated lysophospholipase D activity of glycerophosphodiesterase 7.

Previous studies have shown prostaglandin E2 (PGE2) produced a marked increase in calcitonin secretion in human C-cells derived from medullary thyroid carcinoma. However, it’s unclear whether PGE2 can increase the growth of C cells. In this study, we use TT cells as a C cell model to investigate the effect of PGE2 on the growth of C cells. The results revealed that both PGE2 and arachidonic acid (AA) significantly increased the count of TT cells, whereas indomethacin and Dup697 reduced this count. Notably, an increase in the level of AA was associated with an increase in the number of proliferating TT cells, indicating a dose–response relationship. PGE2 and its receptor agonists (sulprostone and butaprost) enhanced the proliferation of TT cells. By contrast, 17-phenyl-trinor-PGE2 exerted no significant effect on TT cell proliferation, whereas L161982 suppressed it. The positive effect of AA on TT cell proliferation was inhibited by indomethacin, NS398, Dup697 (complete inhibition), and SC560. Both PGE2 and AA increased the level of p-STAT5a. The positive effect of AA on p-STAT5a was completely inhibited by Dup697 but not indomethacin, NS398, or SC560. Treatment with indomethacin or Dup697 alone reduced the level of STAT5a in TT cells. AA increased the level of STAT5a, but this effect was inhibited by indomethacin, NS398, and Dup697. Overall, this study confirms the effect of PGE2 on the proliferation of TT cells. This effect is likely mediated through EP2, EP3, and EP4 receptors and associated with an increase in p-STAT5a level within TT cells.

Clinical evidence suggests the beneficial effects of sumac on cardiovascular risk factors. However, these results are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of sumac supplementation on cardiovascular risk factors in adults. The PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to 30 December 2023 to identify RCTs that were published in English. Data were presented as weighted mean difference (WMD) and associated 95 % confidence interval (CI). The quality of the included trials was measured using the Cochrane Collaboration's modified risk of bias tool. A pooled analysis of 16 trials showed that sumac consumption led to a significant reduction in fasting blood glucose (WMD: −6.03 mg/dl; 95 % CI: −9.67 to −2.39), hemoglobin A1c (WMD: −0.45 %; 95 % CI: −0.59 to −0.31), triglycerides (WMD: −9.07 mg/dL; 95 % CI: −16.19 to −1.94), low-density lipoprotein cholesterol (WMD: −5.58 mg/dL; 95 % CI: −11.27 to −0.12), BMI (WMD: −0.22 kg/m²; 95 % CI: −0.38 to −0.05), weight (WMD: −0.85 kg; 95 % CI: −1.44 to −0.27), waist circumference (WMD: −0.54 cm; 95 % CI: −0.92 to −0.15), and diastolic blood pressure (WMD: −2.72 mmHg; 95 % CI: −4.16 to −1.29). High-density lipoprotein-cholesterol level also increased significantly (WMD: 3.69 mg/dL; 95 % CI: 1.81–5.57). The overall results support possible protective and therapeutic effects of sumac on cardiovascular risk factors in adults. Additional prospective studies are suggested using longer intervention periods and higher supplementation doses to confirm these results.

Background

1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown.

Methods

Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy.

Results

Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA.

Conclusions

Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.

There is controversial data on the impacts of bitter melon (Momordica charantia) supplementations on anthropometric indices. Thus, we aimed to clarify this role of bitter melon through a systematic review, and meta-analysis of the trials. All clinical trials conducted on the impact of bitter melon on anthropometric indices were published until August 2023 in PubMed, Web of Sciences, Scopus, Embase, and Cochrane Library web databases included. Overall, 10 studies with 448 individuals were included in the meta-analysis. Meta-analysis of 10 trials with 448 participants revealed no significant reductions in body weight (BW) (WMD: 0.04 Kg; 95 %CI: −0.16–0.25; P =0.651), body mass index (BMI) (WMD: −0.18 kg/m2; 95 %CI: −0.43–0.07; P =0.171), waist circumference (WC) (WMD: −0.95 cm; 95 % CI: −3.05–1.16; p =0.372), and percentage of body fat (PBF) (WMD: −0.99; 95 % CI: −2.33–0.35; p =0.141) following bitter melon supplementation. There was no significant impact of bitter melon supplementation on BW, BMI, WC, and PBF. More large-scale and high-quality RCTs are necessary to confirm these results.

Specialized pro-resolving mediators (SPMs) are oxidized lipid mediators that have been shown to resolve inflammation in cellular and animal models as well as humans. SPMs and their biological precursors are even commercially available as dietary supplements. It has been understood for more than forty years that pro-inflammatory oxidized lipid mediators, including prostaglandins and leukotrienes, are rapidly inactivated via metabolism. Studies on the metabolism of SPMs are, however, limited. Herein, we report that resolvin D5 (RvD5) and resolvin D1 (RvD1), well-studied SPMs, are readily metabolized by human liver microsomes (HLM) to glucuronide conjugated metabolites. We further show that this transformation is catalyzed by specific uridine 5′-diphospho-glucuronosyltransferase (UGT) isoforms. Additionally, we demonstrate that RvD5 and RvD1 metabolism by HLM is influenced by non-steroidal anti-inflammatory drugs (NSAIDs), which can act as UGT inhibitors through cyclooxygenase-independent mechanisms. The results from these studies highlight the importance of considering metabolism, as well as factors that influence metabolic enzymes, when seeking to quantify SPMs in vivo.

Solid organ transplantation is a life-saving treatment for patients with end-stage organ failure, but it poses unique challenges due to metabolic and immunological changes in recipients. One significant complication is post-transplant diabetes mellitus (PTDM), which affects a variety of solid organ recipients. Leptin, a hormone produced by adipose tissue, regulates appetite and affects glucose metabolism. High leptin levels are associated with the development of PTDM, especially in kidney transplant recipients. Adiponectin, another adipokine, increases insulin sensitivity and has anti-diabetic properties. Low adiponectin levels are associated with insulin resistance and increase the risk of PTDM. As the incidence of PTDM increases due to the increased life expectancy among transplant patients, understanding the role of adipokines such as leptin and adiponectin becomes crucial for early detection and treatment. Additional studies on other adipokines may also provide valuable information on the pathogenesis of PTDM.

The liver plays a central role in systemic metabolism and drug degradation. However, it is highly susceptible to damage due to various factors, including metabolic imbalances, excessive alcohol consumption, viral infections, and drug influences. These factors often result in conditions such as fatty liver, hepatitis, and acute or chronic liver injury. Failure to address these injuries could promptly lead to the development of liver cirrhosis and potentially hepatocellular carcinoma (HCC). Prostaglandin E₂ (PGE₂) is a metabolite of arachidonic acid that belongs to the class of polyunsaturated fatty acids (PUFA) and is synthesized via the cyclooxygenase (COX) pathway. By binding to its G protein coupled receptors (i.e., EP1, EP2, EP3 and EP4), PGE₂ has a wide range of physiological and pathophysiology effects, including pain, inflammation, fever, cardiovascular homeostasis, etc. Recently, emerging studies showed that PGE₂ plays an indispensable role in liver health and disease. This review focus on the research progress of the role of PGE₂ synthase and its receptors in liver physiological and pathophysiological processes and discuss the possibility of developing liver protective drugs targeting the COXs/PGESs/PGE₂/EPs axis.

Several studies indicated the ameliorating effects of flaxseed supplementation on apolipoproteins, although others have conflicting results. Therefore, the present research was conducted in order to accurately and definitively understand the effect of flaxseed on apolipoproteins in adults. All articles published up to Juan 2024 were systematically searched through PubMed, Scopus, Embase, and Web of Science to collect all randomized clinical trials (RCTs). A random effects model was used to measure the combined effect sizes. Also, standardized mean difference (SMD) and 95 % confidence interval (CI) were used to report the combined effect size. Our results showed that flaxseed supplementation significantly reduced apo-BI (SMD: −0.57; 95 % CI: −0.95, −0.19, p = 0.003; I² = 83.2 %, heterogeneity p < 0.001) and lipo(a) decreased (SMD: −0.34; 95 % CI: −0.59, −0.09, p=0.007; I²=30.3 %, heterogeneity p=0.197). However, flaxseed did not change apo-AI levels (SMD: −0.37; 95 % CI: −0.87, 0.13, p = 0.146; I² = 89.2 %, p-heterogeneity < 0.001). This meta-analysis has shown that flaxseed supplementation may have beneficial effects on apolipoproteins. Future high-quality, long-term clinical trials are needed to confirm our results.