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Phytomedicine : International Journal... Jan 2024Amauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with a wide range of medicinal values. Our previous publication demonstrated the...
Protective effect of Amauroderma rugosum ethanol extract and its primary bioactive compound, ergosterol, against acute gastric ulcers based on LXR-mediated gastric mucus secretions.
BACKGROUND
Amauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with a wide range of medicinal values. Our previous publication demonstrated the therapeutic effects of the water extract of A. rugosum (WEA) against gastric ulcers. However, the protective effects of the ethanol extract of A. rugosum (EEA) on gastric mucosa and its major active constituents have not yet been elucidated.
PURPOSE
This study aims to evaluate the gastroprotective effects and underlying mechanisms of EEA and its fat-soluble constituent, ergosterol, in acute gastric ulcers.
STUDY DESIGN AND METHOD
SD rats were pre-treated with EEA (50, 100, and 200 mg/kg) or ergosterol (5, 10, and 20 mg/kg), and acute gastric ulcer models were constructed using ethanol, gastric mucus secretion inhibitor (indomethacin) or pyloric-ligation. The gastric ulcer area, histological structure alterations (H&E staining), and mucus secretion (AB-PAS staining) were recorded. Additionally, Q-PCR, western blotting, immunohistochemistry, ELISA, molecular docking, molecular dynamics simulations, MM-GBSA analysis, and surface plasmon resonance assay (SPR) were used to investigate the underlying mechanisms of the gastroprotective effect.
RESULT
Compared with WEA, which primarily exerts its anti-ulcer effects by inhibiting inflammation, EEA containing fat-soluble molecules showed more potent gastroprotective effect through the promotion of gastric mucus secretion, as the anti-ulcer activity was partly blocked by indomethacin. Meanwhile, EEA exhibited anti-inflammatory effects by suppressing the production of IL-6, IL-1β, TNF-α, and NO, thereby inhibiting the MAPK pathway. Significantly, ergosterol (20 mg/kg), the bioactive water-insoluble compound in EEA, exhibited a gastroprotective effect comparable to that of lansoprazole (30 mg/kg). The promotion of gastric mucus secretion contributed to the effects of ergosterol, as indomethacin can completely block it. The upregulations of COX1-PGE2 and C-fos, an activator protein 1 (AP-1) transcription factor, were observed after the ergosterol treatment. Ergosterol acted as an LXRβ agonist via van der Waals binding and stabilizing the LXRβ protein without compromising its flexibility, thereby inducing the upregulation of AP-1 and COX-1.
CONCLUSION
EEA and its primary bioactive compound, ergosterol, exert anti-ulcer effects by promoting gastric mucus secretion through the LXRβ/C-fos/COX-1/PGE2 pathway.
Topics: Rats; Animals; Stomach Ulcer; Ethanol; Rats, Wistar; Dinoprostone; Molecular Docking Simulation; Transcription Factor AP-1; Rats, Sprague-Dawley; Indomethacin; Mucus; Plant Extracts; Gastric Mucosa; Water; Anti-Ulcer Agents; Polyporaceae
PubMed: 38016383
DOI: 10.1016/j.phymed.2023.155236 -
Scientific Reports Nov 2023Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer...
Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Curcumin; Cyclooxygenase 2; Dinoprostone; Fibroblasts; Inflammation; Cell Line, Tumor; Tumor Microenvironment
PubMed: 38008819
DOI: 10.1038/s41598-023-48073-w -
Taiwanese Journal of Obstetrics &... Nov 2023To evaluate the efficacy and safety of dinoprostone tablet and continuous vaginal insert (Propess®) in low-risk nulliparous women at term with insufficient cervical...
OBJECTIVE
To evaluate the efficacy and safety of dinoprostone tablet and continuous vaginal insert (Propess®) in low-risk nulliparous women at term with insufficient cervical ripening receiving elective induction.
MATERIALS AND METHODS
A retrospective study was conducted between March 2020 and February 2022 and included 230 women who underwent elective induction with dinoprostone tablet or vaginal insert. The primary endpoint was failure of induction. Secondary endpoints included time to vaginal delivery, vaginal delivery rate, as well as maternal and neonatal complications and adverse outcomes.
RESULTS
No statistically significant differences were found between the two groups regarding the main outcome measures; however, the high responders had a significant higher proportion of hyperstimulation and non-reassuring fetal status. The high responder in the Propess group was statistically significant younger (31.68 ± 4.73 vs. 33.82 ± 4.39, p = 0.027), while they had a significantly lower BMI at delivery time of the tablet group (24.49 ± 2.24 vs. 27.42 ± 4.32, p = 0.024). Factors associated with success of vaginal delivery within 24 h (p = 0.015, OR = 0.9, 95%CI = 0.82-0.98) and the Cesarean section (p < 0.001, OR = 1.17, 95%CI = 1.08-1.27) was BMI at delivery time.
CONCLUSION
Slow-release vaginal insert and dinoprostone tablet had similar efficacy and safety for elective induction in low risk nulliparous women at term. Women with younger maternal age or lower BMI at delivery time may have a better response to dinoprostone and had a significantly higher proportion of hyperstimulation and non-reassuring fetal status.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Dinoprostone; Oxytocics; Cesarean Section; Retrospective Studies; Labor, Induced; Administration, Intravaginal; Tablets
PubMed: 38008505
DOI: 10.1016/j.tjog.2023.03.016 -
Medicina (Kaunas, Lithuania) Oct 2023has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the...
has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of against rheumatoid arthritis. The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. The data showed that -treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with down-regulated IL1β, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. In conclusion, possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines.
Topics: Rats; Animals; Rats, Sprague-Dawley; Fragaria; Vascular Endothelial Growth Factor A; Inflammation Mediators; NF-kappa B; Dinoprostone; Arthritis, Experimental; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Plant Extracts; Cytokines; Edema; Matrix Metalloproteinases
PubMed: 38003966
DOI: 10.3390/medicina59111917 -
Prostaglandins, Leukotrienes, and... Dec 2023In bone, prostaglandin E (PGE) is highly osteogenic and formed by osteoblasts, a key modulatory event in the regulation of bone cell activity. MC3T3-E1 cells are widely...
In bone, prostaglandin E (PGE) is highly osteogenic and formed by osteoblasts, a key modulatory event in the regulation of bone cell activity. MC3T3-E1 cells are widely used as an in vitro model of osteoblast function. It is still not clear which pathways contribute to the release of AA in these cells. In this study we have focussed on the contribution of phospholipase D (PLD) enzymes to osteoblastic PGE formation after stimulation with endothelin-1 (ET-1). Using specific inhibitors of PLD1 and PLD2 we could show that PGE formation was strictly dependent on PLD1 but not PLD2 activity and cytosolic phospholipase A (cPLA) was activated by triggering through PLD1. We have identified diacyl glycerol (DAG) as a possible effector molecule which may serve as a triggering signal for PKC activation and subsequent cPLA phosphorylation.
Topics: Animals; Mice; Dinoprostone; Osteoblasts; Phospholipase D; Signal Transduction; Group IV Phospholipases A2; 3T3 Cells
PubMed: 37951067
DOI: 10.1016/j.plefa.2023.102592 -
Irish Journal of Medical Science Jun 2024Dinoprostone vaginal insert is the most common pharmacological method for induction of labor (IOL); however, studies on assessing the time to vaginal delivery (DT)... (Observational Study)
Observational Study
BACKGROUND
Dinoprostone vaginal insert is the most common pharmacological method for induction of labor (IOL); however, studies on assessing the time to vaginal delivery (DT) following dinoprostone administration are limited.
AIMS
We sought to identify the primary factors influencing DT in women from central China, at or beyond term, who underwent IOL with dinoprostone vaginal inserts.
METHODS
In this retrospective observational study, we analyzed the data of 1562 women at 37 weeks 0 days to 41 weeks 6 days of gestation who underwent dinoprostone-induced labor between January 1, 2019, and December 31, 2021. The outcomes of interest were vaginal or cesarean delivery and factors influencing DT, including maternal complications and neonatal characteristics.
RESULTS
Among the enrolled women, 71% (1109/1562) delivered vaginally, with median DT of 740.50 min (interquartile range 443.25 to 1264.50 min). Of the remaining 29% (453/1562), who delivered by cesarean section, 11.9% (54/453) were multiparous. Multiple linear regression analysis showed that multiparity, advanced maternal age, fetal macrosomia, premature rupture of membranes (PROM), and daytime insertion of dinoprostone were the factors that significantly influenced DT. Time to vaginal delivery increased with advanced maternal age and fetal macrosomia and decreased with multiparity, PROM, and daytime insertion of dinoprostone. A mathematical model was developed to integrate these factors for predicting DT: Y = 804.478 - 125.284 × multiparity + 765.637 × advanced maternal age + 411.511 × fetal macrosomia-593.358 × daytime insertion of dinoprostone - 125.284 × PROM.
CONCLUSIONS
Our findings may help obstetricians estimate the DT before placing a dinoprostone insert, which may improve patient management in busy maternity wards and minimize potential risks.
Topics: Humans; Female; Labor, Induced; Retrospective Studies; Dinoprostone; Pregnancy; Adult; Administration, Intravaginal; Oxytocics; Time Factors; Delivery, Obstetric; Cesarean Section
PubMed: 37947994
DOI: 10.1007/s11845-023-03568-3 -
Journal of Animal Science Jan 2023Camelina oil is derived from a low-input, high-yield crop and, in comparison to many other dietary fat sources currently used in equine diets, provides a greater amount...
Effects of dietary camelina, flaxseed, and canola oil supplementation on transepidermal water loss, skin and coat health parameters, and plasma prostaglandin E2, glycosaminoglycan, and nitric oxide concentrations in healthy adult horses.
Camelina oil is derived from a low-input, high-yield crop and, in comparison to many other dietary fat sources currently used in equine diets, provides a greater amount of α-linolenic acid [ALA; (n-3)], than linoleic acid [LA; (n-6)]. However, no research exists assessing the effects of feeding camelina oil to horses in contrast to other commonly used oils. The objective of this study was to compare the effect of supplementing camelina oil to that of flaxseed and canola oil supplementation, on outcomes related to skin and coat health in horses. Thirty adult horses [23 mares, 7 geldings; 14.9 years ± 5.3 years; 544 ± 66 kg body weight (BW) (mean ± SD)] underwent a 4-week wash-in period consuming hay and sunflower oil. Following the wash-in period, horses were blocked by location, age, and BW, and assigned to one of three treatment oils for 16 weeks (370 mg oil/kg BW): camelina (CAM), canola (OLA), or flaxseed (FLX) oil. Blood samples were collected and plasma prostaglandin E2 (PGE2; ELISA), nitric oxide (NO; Griess Reaction), and glycosaminoglycan (GAG; DMMB) concentrations were measured on weeks 0 (n = 30), 14 (n = 24), and 16 (n = 30). On weeks 0, 2, 4, 8, and 16, transepidermal water loss (TEWL) was measured pre- and post-acetone application using a VapoMeter (n = 26), and a 5-point-Likert scale was used to assess skin and coat characteristics on the side and rump of the horses (n = 30). All data were analyzed with repeated measures ANOVA using PROC GLIMMIX in SAS. Independent of treatment, coat color, and quality increased from baseline. There were no differences in the outcomes assessed between the horses supplemented camelina oil and those supplemented canola or flaxseed oil. These results suggest that independent of treatment, all oil supplements improved coat color and quality in horses. This provides indication that camelina oil is comparable to existing plant-based oil supplements in supporting skin and coat health and inflammation in horses.
Topics: Animals; Horses; Male; Female; Flax; Dinoprostone; Rapeseed Oil; Nitric Oxide; Water; Glycosaminoglycans; Diet; Dietary Supplements; Linseed Oil; Plant Oils; Fatty Acids, Omega-3
PubMed: 37935917
DOI: 10.1093/jas/skad373 -
Scientific Reports Nov 2023Exposure to particulate matter (PM) causes mitochondrial dysfunction and lung inflammation. The cyclooxygenase-2 (COX-2) pathway is important for inflammation and...
Exposure to particulate matter (PM) causes mitochondrial dysfunction and lung inflammation. The cyclooxygenase-2 (COX-2) pathway is important for inflammation and mitochondrial function. However, the mechanisms by which glucocorticoid receptors (GRs) suppress COX-2 expression during PM exposure have not been elucidated yet. Hence, we examined the mechanisms underlying the dexamethasone-mediated suppression of the PM-induced COX-2/prostaglandin E2 (PGE2) pathway in A549 cells. The PM-induced increase in COX-2 protein, mRNA, and promoter activity was suppressed by glucocorticoids; this effect of glucocorticoids was antagonized by the GR antagonist RU486. COX-2 induction was correlated with the ability of PM to increase reactive oxygen species (ROS) levels. Consistent with this, antioxidant treatment significantly abolished COX-2 induction, suggesting that ROS is involved in PM-mediated COX-2 induction. We also observed a low mitochondrial membrane potential in PM-treated A549 cells, which was reversed by dexamethasone. Moreover, glucocorticoids significantly enhanced Bcl-2/GR complex formation in PM-treated A549 cells. Glucocorticoids regulate the PM-exposed induction of COX-2 expression and mitochondrial dysfunction and increase the interaction between GR and Bcl-2. These findings suggest that the COX-2/PGE2 pathway and the interaction between GR and Bcl-2 are potential key therapeutic targets for the suppression of inflammation under PM exposure.
Topics: Humans; Glucocorticoids; Cyclooxygenase 2; Dexamethasone; A549 Cells; Particulate Matter; Dinoprostone; Reactive Oxygen Species; Inflammation
PubMed: 37919369
DOI: 10.1038/s41598-023-46257-y -
Nature Nov 2023Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies. Inflammatory and immunomodulatory signals co-exist in the pancreatic...
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies. Inflammatory and immunomodulatory signals co-exist in the pancreatic tumour microenvironment, leading to dysregulated repair and cytotoxic responses. Tumour-associated macrophages (TAMs) have key roles in PDAC, but their diversity has prevented therapeutic exploitation. Here we combined single-cell and spatial genomics with functional experiments to unravel macrophage functions in pancreatic cancer. We uncovered an inflammatory loop between tumour cells and interleukin-1β (IL-1β)-expressing TAMs, a subset of macrophages elicited by a local synergy between prostaglandin E (PGE) and tumour necrosis factor (TNF). Physical proximity with IL-1β TAMs was associated with inflammatory reprogramming and acquisition of pathogenic properties by a subset of PDAC cells. This occurrence was an early event in pancreatic tumorigenesis and led to persistent transcriptional changes associated with disease progression and poor outcomes for patients. Blocking PGE or IL-1β activity elicited TAM reprogramming and antagonized tumour cell-intrinsic and -extrinsic inflammation, leading to PDAC control in vivo. Targeting the PGE-IL-1β axis may enable preventive or therapeutic strategies for reprogramming of immune dynamics in pancreatic cancer.
Topics: Humans; Carcinogenesis; Carcinoma, Pancreatic Ductal; Dinoprostone; Disease Progression; Gene Expression Regulation, Neoplastic; Inflammation; Interleukin-1beta; Pancreatic Neoplasms; Tumor Microenvironment; Tumor Necrosis Factors; Tumor-Associated Macrophages
PubMed: 37914939
DOI: 10.1038/s41586-023-06685-2 -
International Journal of Molecular... Oct 2023In this study, we confirmed that thrombin significantly increases the production of COX-2 and PGE in human tracheal smooth muscle cells (HTSMCs), leading to inflammation...
In this study, we confirmed that thrombin significantly increases the production of COX-2 and PGE in human tracheal smooth muscle cells (HTSMCs), leading to inflammation in the airways and lungs. These molecules are well-known contributors to various inflammatory diseases. Here, we investigated in detail the involved signaling pathways using specific inhibitors and small interfering RNAs (siRNAs). Our results demonstrated that inhibitors targeting proteins such as protein kinase C (PKC)δ, proline-rich tyrosine kinase 2 (Pyk2), c-Src, epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), or activator protein-1 (AP-1) effectively reduced thrombin-induced COX-2 and PGE production. Additionally, transfection with siRNAs against PKCδ, Pyk2, c-Src, EGFR, protein kinase B (Akt), or c-Jun mitigated these responses. Furthermore, our observations revealed that thrombin stimulated the phosphorylation of key components of the signaling cascade, including PKCδ, Pyk2, c-Src, EGFR, Akt, and c-Jun. Thrombin activated COX-2 promoter activity through AP-1 activation, a process that was disrupted by a point-mutated AP-1 site within the COX-2 promoter. Finally, resveratrol (one of the most researched natural polyphenols) was found to effectively inhibit thrombin-induced COX-2 expression and PGE release in HTSMCs through blocking the activation of Pyk2, c-Src, EGFR, Akt, and c-Jun. In summary, our findings demonstrate that thrombin-induced COX-2 and PGE generation involves a PKCδ/Pyk2/c-Src/EGFR/PI3K/Akt-dependent AP-1 activation pathway. This study also suggests the potential use of resveratrol as an intervention for managing airway inflammation.
Topics: Humans; CSK Tyrosine-Protein Kinase; Cyclooxygenase 2; Dinoprostone; ErbB Receptors; Focal Adhesion Kinase 2; Inflammation; Myocytes, Smooth Muscle; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Resveratrol; src-Family Kinases; Thrombin; Transcription Factor AP-1
PubMed: 37894811
DOI: 10.3390/ijms242015130