Prostaglandins & other lipid mediators最新文献

Eczema is also known as atopic dermatitis, which goes on to affect the skin as a chronic inflammatory disease. It is associated with a constant feeling of scratchiness, erthyma and disruption of the natural skin barrier. Treatment provided at present may improve some of the symptoms, for instance use of corticosteroids or immunosuppressive agents, however, there is an overwhelming need for better focused and effective methods of treatment with minimal adverse effects. Fevipiprant, a DP2 receptor antagonist, has emerged as a promising agent targeting prostaglandin D2 (PGD2) pathways, which play a crucial role in eczema pathophysiology. This review examines the mechanism of action, pharmacological profile of Fevipiprant and present studies on preclinical and clinical development of Fevipiprant for treatment of eczema. Additionally, we provide a comparison of Fevipiprant with existing treatment options and evaluate its safety and tolerability. The evaluation gives a reason that targeting in the treatment of eczema by the use of Fevipiprant is able to effectively target the DP2 pathway which is associated with a good safetyl however presenting itself as a new treatment option in the management of eczema. Finally, long-term studies are essential to validate the feasibility, safety, and effectiveness of Fevipiprant compared to existing therapies for eczema. Novartis has taken advantage of this stat for comp… given the scarcity of effective therapies for paediatric atopic dermatitis in Japan. Exploring Fevipiprant from the Efficacy Perspective is also required because it will impact how it will enter clinical practice in therapy of eczema in the future.

Unresolved chronic inflammation, a hallmark of cancer, promotes tumor growth and metastasis in various cancer types. In contrast to blocking inflammation, stimulation of resolution of inflammation is an entirely novel approach to "resolve" inflammation. Resolution of inflammation mechanisms in cancer includes clearance of tumor debris, counter-regulation of pro-inflammatory eicosanoids and cytokines, and suppression of leukocyte infiltration. Conventional cytotoxic chemotherapy, radiation, anti-angiogenic therapy, and immune checkpoint inhibitors directly or indirectly can lead to the generation of pro-tumorigenic cellular debris. Over the past two decades, a potential paradigm shift has emerged in the inflammation field with the discovery of specialized pro-resolving mediators (SPMs), including resolvins, lipoxins, maresins, and protectins. SPMs are structurally distinct families of mediators grouped together by their pro-resolving "debris-clearing" functions. "Pro-resolving" therapies are in clinical development for various inflammation-driven diseases, including cancer. SPMs, as novel cancer therapeutics, have tremendous potential to enhance current cancer therapy. The mechanisms of SPMs as anti-cancer therapeutics are under active investigation by various laboratories worldwide. Here, we explore the current appreciation of the SPMs as innovative potential treatments designed to harness the unique anti-cancer activity of SPMs.

Several meta-analyses have examined the effect of Nigella sativa (N. Sativa) supplementation on inflammatory and oxidative markers, with conflicting results. So, the current study evaluated the effect of N. Sativa on some oxidative and inflammatory parameters. The Embase, Web of Science, Scopus, PubMed databases, and Google Scholar were systemically searched to identify papers indexed before February 2023. The pooled results were calculated with the use of a random-effects model to evaluate the effects of N. Sativa on inflammatory and oxidative markers. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Overall, seven meta-analyses were included in the study. N. Sativa supplementation significantly decreased serum C-reactive protein (CRP) (ES = -0.42; 95 % CI: -0.58, -0.25, p < 0.001), tumor necrosis factor-alpha (TNF-α) (ES= -1.27; 95 % CI: -2.29, -0.25; p = 0.015), and malondialdehyde (MDA) (ES = -0.67; 95 % CI: -0.97, -0.36, p < 0.001) levels, and significantly improved total antioxidant capacity (TAC) (ES = 0.34; 95 % CI: 0.20, 0.47, p < 0.001) and superoxide dismutase (SOD) (ES = 50.66; 95 % CI: 34.15, 67.18, p < 0.001) levels. N. Sativa supplementation had beneficial effects on CRP, TNF-α, MDA, SOD, and TAC. Thus, N. Sativa can be recommended as an adjuvant anti-inflammatory and anti-oxidant agent.

Objectives: This study aims to determine the levels of TNF-α, IGF-1, IL-6, and IL-10 protein in blood samples and their potential link to bronchitis-asthma diseases in the Iraq Duhok population, highlighting the prevalence of these long-term inflammatory diseases.

Methods: Sixty blood samples were used and separated into patients (n = 43) and control (n = 17) groups. Serum samples were separated for each individual. Elisa method was used in terms of 4 different proteins investigated in blood samples with the manufacturer's instruction brand kits.

Results: This study evaluated TNF-α, IGF-1, IL-6, and IL-10 protein levels in blood samples from asthmatic bronchitis patients in Duhok. Although these levels were elevated compared to controls, the differences were not statistically significant.

Conclusion: The differences thought to be related to the bronchitis-asthma diseases could not be demonstrated between the patient and control groups in Iraq Duhok population. Future research should explore larger sample sizes and stratified patient groups to identify potential biomarkers.

Objective: Dravet syndrome is a severe, intractable epilepsy in which 80 % of patients have a de novo mutation in the gene SCN1A. We recently reported that a high seizure burden increased hippocampal concentrations of an array of pro-inflammatory prostaglandins in the Scn1a^+/- mouse model of Dravet syndrome. This raised the possibility that a high seizure burden might also trigger the accumulation of specialized pro-resolving mediators that facilitate the resolution of neuroinflammation and brain repair. The present study therefore aimed to examine whether a high seizure burden increased hippocampal concentrations of various specialized pro-resolving mediators in the Scn1a^+/- mouse model of Dravet syndrome.

Methods: Scn1a^+/- mice at postnatal day 21 (P21) were primed with a single hyperthermia-induced seizure event to induce a high seizure burden. On P24 primed Scn1a^+/- mice with a high seizure burden, unprimed naïve Scn1a^+/- mice and wild-type (WT) mice were euthanized and hippocampal tissue was collected for analysis of various specialized pro-resolving mediators using liquid chromatography mass spectrometry.

Results: Scn1a^+/- mice with a high seizure burden showed increased hippocampal concentrations of the pro-inflammatory leukotrienes B4 and E4. Further, a high seizure burden increased hippocampal concentrations of various special pro-resolving mediators, including the maresins (maresin1), D-series resolvins (RVD1 and RVD4), and protectin (PCTR1). To further characterize these changes, we determined the mRNA expression of lipoxygenase genes, as these synthetic enzymes are common across classes of specialized pro-resolving mediators. However, hippocampal expression of Alox5, Alox12 and Alox15 were not influenced by a high seizure burden.

Significance: We report for the first time that a high seizure burden increases the hippocampal concentrations of various specialized pro-resolving mediators in Scn1a^+/- mice. This provides a platform for future studies to examine whether modulation of these mediators might be exploited to reduce seizures and facilitate brain repair in intractable epilepsy syndromes.

Background: There is no consensus in the existing literature regarding the effect of soluble fiber on the lipid profile of patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis of randomized controlled trials aimed to assess the effect of soluble fiber on triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in T2DM patients.

Methods: PubMed/MEDLINE, Scopus, and ISI Web of sciences were searched for RCTs up to 4 May 2024. Data from RCTs were pooled using the generic inverse variance method and expressed as weighted mean differences (WMD) with 95 % confidence interval (CIs).

Results: Pooled data from 38 RCTs reporting patient outcomes were evaluated for mean effects. Results indicated that soluble fiber significantly altered TG (WMD: -16.97 mg/dL, 95 % CI: -29.16 to -4.78, P = 0.021), HDL-C (WMD: 1.74 mg/dL, 95 % CI: 1.02-2.46, P < 0.001), LDL-C (WMD: -11.14 mg/dL, 95 % CI: -15.41 to -6.87, P < 0.001), and TC (WMD: -13.87 mg/dL, 95 % CI: -17.99 to -9.75, P = 0.027).

Conclusions: Soluble fiber supplementation has the potential to improve lipid profile in patients with T2DM, and may provide a feasible approach for improving metabolic health in T2DM patients.

Background: Tumor metastasis is the main cause of death in lung adenocarcinoma (LAC) patients. It is known that the collagen triple helix repeats containing 1 (CTHRC1) protein is implicated in tissue remodeling and is tightly linked to the carcinogenesis and metastasis of solid tumors. However, the functional role of CTHRC1 and its potential mechanisms in LAC cell metastasis have not been fully explored.

Methods: The expression level of CTHRC1 in LAC was measured by using bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB). Small interfering RNA and overexpression methods were employed to investigate the function and molecular mechanisms of CTHRC1 in LAC cells. Through bioinformatics analysis, qRT-PCR, WB, scratch healing assay, Transwell, assay kits, and flow cytometry, the downstream pathways and upstream regulatory genes of CTHRC1 in LAC cells were investigated. The binding sites were verified by using chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene experiments.

Results: In this project, CTHRC1 was found to be abnormally upregulated in LAC tissues and cells. CTHRC1 promoted the migration and invasion of LAC cells. The promoting effect of CTHRC1 overexpression on LAC cell migration was weakened after the addition of orlistat (a fatty acid synthase inhibitor). Mechanistically, TF AP-2α (TFAP2A) was directly bound to the upstream sequence of the CTHRC1 promoter and promoted CTHRC1 expression. The TFAP2A-CTHRC1 axis induced the migration of LAC cells by activating fatty acid metabolism.

Conclusion: Our results indicated that TFAP2A activates fatty acid metabolism by positively modulating the expression of CTHRC1, thereby facilitating tumor cells' migration and invasion. These findings provided novel insights into LAC treatment and future research.

Knee osteoarthritis (KOA) refers to a prevalent musculoskeletal disorder, frequently complicated by substantial pain and physical disability. Yougui Yin (YGY) is a classic Chinese herbal mixture which has demonstrated potential in treating KOA. Considering that, its cryptic mechanism warrants to be deciphered, which is the subject of our present research. In vivo, H&E staining, Alcian blue staining and Masson staining assessed the histomorphology. Commercial kits and ELISA evaluated oxidative stress markers. ELISA also assayed serum inflammatory cytokines. TUNEL staining appraised apoptosis. Western blotting examined cartilage matrix degradation, apoptotic and NLRP3 inflammasome proteins. Immunofluorescence assay estimated macrophage polarization. In vitro, ELISA assayed oxidative stress markers and inflammatory cytokines. Immunofluorescence and flow cytometry assay estimated macrophage polarization. MTT and flow cytometry assays severally measured cell viability and apoptosis. DCFH-DA probe detected ROS formation. RT-qPCR and Western blotting examined chondrocyte markers, apoptotic and pyroptotic genes. YGY significantly eased the histomorphological damage, apoptosis and pyroptosis in the cartilage tissues of KOA mice. Besides, YGY exerted anti-oxidant and anti-inflammatory activities and drove M1-to-M2 polarization of macrophages both in vitro and in vivo. Further, the co-culture of macrophages treated by LPS and serum containing YGY improved the viability, eliminated the apoptosis, pyroptosis, inflammation, oxidative stress and cartilage degradation in TNF-α-exposed chondrocytes co-cultured with LPS-intervened macrophages. Overall, YGY might mediate macrophage polarization to impede the advancement of KOA.

Background and aim: Previous studies have reported on the relationship between vitamin D and the lipid profile in individuals with obesity or overweight, but results have been inconsistent. Hence, we conducted this meta-analysis and systematic review of randomized controlled trials to assess the effect of vitamin D on the lipid profile in individuals with overweight or obesity.

Methods: A meticulous search strategy was used in various databases, and article published up to November 2023 were included. The DerSimonian and Laird random effects model was applied to compute the weighted mean difference (WMD) and 95 % confidence intervals (CI) of the intervention on each variable.

Results: Vitamin D supplementation did not yield significant alterations in LDL-C (WMD: 2.10 mg/dL, CI: -5.20-9.41, p = 0.572), HDL-C (WMD: 1.49 mg/dL, 95 % CI: -1.55-4.55, P = 0.337), and TC concentrations (WMD: -1.99 mg/dL, CI: -8.21-4.22, P = 0.530). Conversely, a significant decrease in TG levels was observed studies conducted in individuals with comorbidities (WMD: -6.03 mg/dL, 95 % CI: -11.92 to -0.15, p = 0.044), vitamin D doses of ≥ 50000 IU/week (WMD: -20.87 mg/dL, 95 % CI: -39.63 to -2.11, P = 0.029), and subjects with baseline TG concentrations ≥ 150 mg/dl (WMD: -25.95 mg/dL, 95 % CI: -51.51 to -0.40, p = 0.046).

Conclusion: According to our study findings, vitamin D has significant effect on the hypertriglyceridemia in individuals with obesity or overweight. However, vitamin D has no significant effect on the LDL-C, HDL-C, and TC concentrations in individuals with obesity or overweight.

Introduction: Aberrant vascular function and cancer growth are closely related, with nitric oxide (NO) being a key factor in vascular tone regulation. This study provides Novel insights into the distinctive mechanisms underlying cancer-associated vascular dysfunction by investigating the involvement of potassium (K⁺) channels in NO-mediated vasorelaxation within arteries supplying colon cancer.

Methods: Arterial segments from colon cancer patients were isolated and sectioned into rings, these rings were mounted in an organ bath filled with Krebs' solution and maintained at 37°C. Isometric tension recordings were obtained using a force transducer connected to a PowerLab Data Acquisition System. Arterial segments were pre-incubated with a variety of K⁺ channel blockers, both individually and in combination, including glibenclamide (GLIB), barium chloride (BaCl₂), tetraethylammonium (TEA), and 4-aminopyridine (4-AP). Concentration-response curves were designed to evaluate how K⁺ channel blocking affected the vasodilation caused by NO.

Results: Sodium nitroprusside (SNP) induced vasorelaxation in arterial rings from colon cancer, influenced by specific K+ channels. Pre-incubation with TEA significantly reduced Emax to 60.22 ± 8.14 %, compared to 124.91 ± 15.07 % in controls, while GLIB decreased Emax to 113.10 ± 3.87 %. BaCl2 and 4-AP further diminished relaxation, and combined K⁺ channel blockers showed complex, non-additive effects. Distinct contributions of K_Ca and K_V channels to NO-induced vasodilation were elucidated. Additionally, interaction between NO and L-type calcium (Ca²⁺) channels suggested a novel vasorelaxation mechanism in cancerous tissues.

Conclusion: This research offers new perspectives on the intricate relationship between vascular biology and cancer development, emphasizing the promise of targeting potassium channels to address vascular abnormalities in cancer.