Prostaglandin E2 Production Research Articles

Multi-omics reveal the metabolic patterns in mouse cumulus cells during oocyte maturation

Bi-directional communication between cumulus cells and the surrounded oocytes is important for the development and functions of both compartments. However, the metabolic framework in cumulus cells has not been systematically described. In the present study, cumulus cells from cumulus-oocyte complexes (COCs) at three key time points were isolated (arrested GV stage, post-hCG 0h; meiotic resumption GVBD stage, post-hCG 3h; and metaphase II stage, post-hCG 12h), and the temporal metabolomic and proteomic profiling were performed. Integrated multi-omics analysis reveals the global metabolic patterns in cumulus cells during mouse oocyte maturation. In particular, we found the active hyaluronic acid metabolism, steroid hormone synthesis, and prostaglandin E2 (PGE2) production in cumulus cells. Meanwhile, accompanying the oocyte maturation, a progressive increase in nucleotide and amino acid metabolism was detected in the surrounding cumulus cells. In sum, the data serve as a valuable resource for probing metabolism during terminal differentiation of ovarian granulosa cells, and provide the potential biomarkers for improving and predicting oocyte quality.

Elucidating the Anti-Inflammatory Properties of Garcinia kola and Vernonia amygdalina through in silico Molecular Biology Techniques

Introduction: Inflammation is implicated in many disorders, including communicable and noncommunicable diseases. Cyclooxygenase-2 (Cox-2) is a key enzyme involved in the production of prostaglandins implicated in inflammatory disorders. Garcinia kola and Vernonia amygdalina are medicinal plants being used for treating various ailments in many parts of the world and extensive in vitro and in vivo studies have been conducted on them. Five phytochemicals were selected from the two plants; aspirin and celecoxib were used as reference drugs. This study investigated the interactions of the seven ligands with the Cox-2 enzyme, using in silico molecular biology techniques. Materials and Methods: The 3-D structures of the seven ligands were retrieved from the PubChem database in their Structure Data Format (SDF). Cox-2 was retrieved in its Protein Data Bank (PDB) format. The ligands and the protein were converted to their pdbqt formats through the open babel software. The Cox-2 was docked with the ligands using the Auto-Dock Vina software. The binding energies and the root mean square deviation values were noted. Pharmacophore modeling was visualized by using the Biovia Discovery Studio Visualizer. One of the ligands (luteolin) was further subjected to molecular dynamics simulation using the desmond maestro software. Results: While celecoxib had the best binding property with Cox-2 (-10.8 kcal/mol, 3 H bonds), the five ligands from the two plants had better binding properties than aspirin (which had -6.5kcal/mol, 1 H bond). Kolaviron, from G. kola (-9.1 kcal/mol, 3 H bonds) and luteolin, from V. amygdalina (-8.5kcal/mol, 2 H bonds) demonstrated the best binding properties among the five phytochemicals. Additional interactions of H bonds and hydrophobic bonds were noticed post molecular dynamics simulation of luteolin with Cox-2, indicating dynamic forces’ fluctuations. MD simulations showed that Ser530 and Tyr385 were the best amino acid side chains that interacted with luteolin for the stabilization of the protein-ligand complex. Conclusion: The energy values and protein-ligand interactions indicate affinity and stability of the complex. Luteolin can be taken as a promising drug target and subjected to ADMET (absorption, distribution, metabolism, excretion, toxicity) properties analysis and clinical trials. This is especially important in view of the various side effects associated with both nonselective and selective Cox-2 inhibitors, including aspirin and celecoxib.

The mechanisms related to fibroblasts in burn surface.

Mesenchymal stem cells (MSCs) can promote burn wound healing, skin appearance, and function recovery by promoting the differentiation and migration of fibroblasts of a wound. The burn environment can activate the autophagy of MSCs. However, it is not clear whether this autophagy can affect the proliferation and migration of fibroblasts. In this study, pretreated MSCs with rapamycin and 3-methyladenine modulated autophagy and co-cultured with fibroblasts of burn. Cell migration was detected by immunofluorescence chemical staining. Western blot analysis and enzyme-linked immunosorbent assay were performed to detect 2,3-Dioxygenase (IDO), cytokine synthesis inhibitory factor 10 (IL-10), cytokine synthesis inhibitory factor 6 (IL-6), prostaglandin E2 (PGE2), transforming growth factor beta 1 (TGF-β1) proteins levels, and the autophagy proteins p62 and microtubule-associated protein LC3-II/I. We demonstrated that autophagy regulates MSCs survival and proliferation in burn wound transplants and found that autophagy inhibition with 3-methyladenine reduced MSCs-mediated, fibroblast proliferation and migration in burn environment. However, rapamycin-induced autophagy had the opposite effect and increased the TGF-β1 expression. Therefore, we speculate that MSCs may promote fibroblast proliferation and migration by secreting TGF-β1 via the AKT/mTOR (RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin) pathway. Autophagy of MSCs regulates burn wound fibroblast proliferation and migration by affecting TGF-β1 and prostaglandin E2 production adjacent to MSCs transplanted on the burn wound. The results of this study provide a potential strategy for promoting MSCs treatment of burns.

Protective effect of fustin against adjuvant-induced arthritis through the restoration of proinflammatory response and oxidative stress.

Rheumatoid arthritis causes irreparable damage to joints. The present research sought to check fustin's anti-arthritic efficacy against the complete Freund's adjuvant-induced arthritis paradigm in animals by altering the inflammatory response. In the rats, complete Freund's adjuvant was used to trigger arthritis and they received fustin at 50 and 100 mg/kg for 21 days. At regular intervals, the hind paw volume and arthritic score were assessed. After the trial period, hematological, antioxidant, pro-inflammatory cytokines, and other biochemical parameters were estimated. Fustin-treated rats showed the down-regulation of hind paw volume, arthritic score, and altered hematological parameters (TLC, DLC (neutrophil, lymphocyte, monocyte, eosinophil, basophil)). Furthermore, fustin significantly mitigates proinflammatory cytokine (reduced interleukin, tumor necrosis factor-a (TNF-α), IL-6, IL-1β), oxidative stress (attenuated malondialdehyde (MDA), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD)), attenuated production of prostaglandin E2 and myeloperoxidase (MPO) and improved nuclear factor erythroid 2-related factor (Nrf2) action. Fustin led to the benefit in arthritis-prone animals elicited by complete Freund's adjuvant via pro-inflammatory cytokine.

Protocatechuic Acid and Syringin from Saussurea neoserrata Nakai Attenuate Prostaglandin Production in Human Keratinocytes Exposed to Airborne Particulate Matter.

Saussurea neoserrata Nakai offers a reliable and efficient source of antioxidants that can help alleviate adverse skin reactions triggered by air pollutants. Air pollutants, such as particulate matter (PM), have the ability to infiltrate the skin and contribute to the higher occurrence of cardiovascular, cerebrovascular, and respiratory ailments. Individuals with compromised skin barriers are particularly susceptible to the impact of PM since it can be absorbed more readily through the skin. This study investigated the impact of protocatechuic acid and syringin, obtained from the n-BuOH extract of S. neoserrata Nakai, on the release of PGE2 and PGD2 induced by PM10. Additionally, it examined the gene expression of the synthesis of PGE2 and PGD2 in human keratinocytes. The findings of this research highlight the potential of utilizing safe and efficient plant-derived antioxidants in dermatological and cosmetic applications to mitigate the negative skin reactions caused by exposure to air pollution.

Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review.

Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentiallyeffective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients.Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles(SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for cross-sectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.

Evaluation of Renoprotective Effect of Lipoic Acid and Bosentan Against Diclofenac-Induced Acute Renal Failure

Acute renal failure also known as acute kidney injury (AKI) is a complex health condition related to significant morbidity and mortality. In hospitalized patients, around 19-33 percent of AKI episodes are linked to drug induced nephrotoxicity. Although considered safe, NSAIDs such as diclofenac have gained special attention over the past few years due to the potential risk of renal injury. The direct effect of diclofenac-induced renal injury depends on targeting the mitochondria in kidney tissue, and formation of reactive oxygen species (ROS) resulting in oxidative stress. Secondly, diclofenac inhibit renal prostaglandin production, limiting renal afferent arteriole vasodilation, increasing afferent resistance; thus decreasing the glomerular capillary pressure below normal values and glomerular filtration rate will decrease resulting in AKI. Alpha-Lipoic acid (ALA) has beneficial effects in prevention or relief of symptoms of oxidative stress- related diseases, as it acts as antioxidant and anti-inflammatory micronutrient. Bosentan is a competitive antagonist with dual endothelin-1 receptors, as renal vascular ET-1 system is upregulated under many pathophysiological situations. In present study, we investigated the effect of lipoic acid and bosentan in diclofenac induced acute renal failure in male rats.
 We observed that diclofenac increased serum levels of urea, creatinine, malondialdehyde, KIM-1, TGFβ1 and fibronectin significantly (p>0.05) in the induction group compared to control group. While, SOD significantly (p>0.05) reduced in the induction group compared to control group. Both of lipoic acid and bosentan alone didn’t significantly protect against diclofenac induced AKI. However, the combination group showed a significant protection against AKI. Pearson correlation analysis showed a significant positive correlation between (urea and KIM-1) and between (creatinine and KIM-1) (r2=0.792 and r2=0.677 respectively). Furthermore, there was a significant positive correlation between fibronectin and urea (r2= 0.498, p>0.01) and fibronectin and creatinine (r2=0.356, p>0.05). Interestingly, KIM-1 showed a significant positive correlation with fibronectin (r2=0.536, p>0.01).
 ROC curve test was performed for KIM-1 and fibronectin biomarkers. The AUC for KIM-1 was 0.986 and for fibronectin was 0.829. We concluded that combination therapy of lipoic acid and bosentan showed a significant protective effect against diclofenac-induced AKI. In addition, fibronectin could be a promising biomarker for detection and diagnosis of acute kidney injury.
 Key words: Diclofenac, oxidative stress, alpha- lipoic acid, endothelin-1, bosentan

Smooth muscle dysfunction in the pre-inflammation site in stenotic Crohn's-like colitis: implication of mechanical stress in bowel dysfunction in gut inflammation.

Background and Aims: Gut smooth muscle dysfunctions contribute to symptoms such as abdominal cramping, diarrhea, and constipation in inflammatory bowel disease (IBD). The mechanisms for muscle dysfunctions are incompletely understood. We tested the hypothesis that mechanical stress plays a role in muscle dysfunction in a rat model of Crohn's-like colitis where inflammatory stenosis leads to mechanical distention in the pre-inflammation site. Methods: Crohn's-like colitis was induced by intracolonic instillation of TNBS (65mg/kg) in Sprague-Dawley rats. Control rats were instilled with saline. The rats were fed with either regular solid food or exclusively liquid diet. Rats were euthanized by day 7. Results: When rats were fed with solid food, TNBS treatment induced localized transmural inflammation with stenosis in the instillation site and marked distention with no inflammation in the pre-inflammation site of the colon. Smooth muscle contractility was suppressed, and expression of cyclo-oxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2) were increased not only in the inflammation site but also in the pre-inflammation site. Liquid diet treatment, mimicking exclusive enteral nutrition, completely released mechanical distention, eliminated COX-2 expression and PGE2 production, and improved smooth muscle contractility especially in the pre-inflammation site. When rats were administered with COX-2 inhibitor NS-398 (5mg/kg, i. p. daily), smooth muscle contractility was restored in the pre-inflammation site and significantly improved in the inflammation site. Conclusion: Colonic smooth muscle contractility is significantly impaired in stenotic Crohn's-like colitis rats not only in the inflammation site, but in the distended pre-inflammation site. Mechanical stress-induced expression of COX-2 plays a critical role in smooth muscle dysfunction in the pre-inflammation site in Crohn's-like colitis rats.

Anti-inflammatory effect of 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole derivatives as p38α inhibitors

In the present work, the anti-inflammatory effect of 30 compounds containing 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole was investigated. All final target compounds showed significant Inhibitory effect on p38α. P38α is considered one of the key kinases in the inflammatory process due to its regulatory effect on pro-inflammatory mediators. The final target compounds divided into four group based on the type of terminal moiety (amide and sulfonamide) and the linker between pyrimidine ring and terminal moiety (ethyl and propyl). Most compounds with terminal sulfonamide moiety and propyl linker between the sulfonamide and pyrimidine ring were the most potent among all synthesized final target compounds with sub-micromolar IC50s. Compound 24g (with p-Cl benzene sulfonamide and propyl linker) exhibited the highest activity over P38α with IC50 0.68 µM. All final target compounds were tested for their ability to inhibit nitric oxide release and prostaglandin E2 production. Compounds having amide terminal moiety with ethyl linker showed higher inhibitory activity for nitric oxide release and compound 21d exhibited the highest activity for nitric oxide release with IC50 1.21 µM. Compounds with terminal sulfonamide moiety and propyl linker showed the highest activity for inhibiting PGE2 production and compounds 24i and 24g had the lowest IC50s with value 0.87 and 0.89 µM, respectively. Compounds 21d, 22d and 24g were tested for their ability to inhibit over expression of iNOS, COX1, and COX2. In addition the ability of compounds 21d, 22d and 24g to inhibit inflammatory cytokines were determined. Finally molecular docking of the three compounds were performed on P38α crystal structure to expect their mode of binding.

Anti-oxidant and Anti-inflammatory Effects of Ethanol Extract from Polygala sibirica L. var megalopha Fr. on Lipopolysaccharide-Stimulated RAW264.7 Cells.

To investigate the anti-oxidant and anti-inflammatory effects of ethanol extract of Polygala sibirica L. var megalopha Fr. (EEP) on RAW264.7 mouse macrophages. RAW264.7 cells were pretreated with 0-200 µg/mL EEP or vehicle for 2 h prior to exposure to 1 µg/mL lipopolysaccharide (LPS) for 24 h. Nitric oxide (NO) and prostaglandin (PGE2) production were determined by Griess reagent and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1beta (IL-1β), and IL-6 were determined using reverse transcription polymerase chain reaction (RT-PCR). Western blot assay was used to determine the protein expressions of iNOS, COX-2, phosphorylation of extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK), inhibitory subunit of nuclear factor Kappa B alpha (Iκ B-α) and p38. Immunofluorescence was used to observe the nuclear expression of nuclear factor-κ B p65 (NF-κ B p65). Additionally, the anti-oxidant potential of EEP was evaluated by reactive oxygen species (ROS) production and the activities of catalase (CAT) and superoxide dismutase (SOD). The 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), superoxide anion (O2-) radical and nitrite scavenging activity were also measured. The total polyphenol and flavonoid contents of EEP were 23.50±2.16 mg gallic acid equivalent/100 g and 43.78±3.81 mg rutin equivalent/100 g. With EEP treatment (100 and 150 µg/mL), there was a notable decrease in NO and PGE2 production induced by LPS in RAW264.7 cells by downregulation of iNOS and COX-2 mRNA and protein expressions (P<0.01 or P<0.05). Furthermore, with EEP treatment (150 µg/mL), there was a decrease in the mRNA expression levels of TNF-α, IL-1β and IL-6, as well as in the phosphorylation of ERK, JNK and p38 mitogen-activated protein kinase (MAPK, P<0.01 or P<0.05), by blocking the nuclear translocation of NF-κ B p65 in LPS-stimulated cells. In addition, EEP (100 and 150 µg/mL) led to an increase in the anti-oxidant enzymes activity of SOD and CAT, with a concomitant decrease in ROS production (P<0.01 or P<0.05). EEP also indicated the DPPH, OH, O2- radical and nitrite scavenging activity. EEP inhibited inflammatory responses in activated macrophages through blocking MAPK/NF-κ B pathway and protected against oxidative stress.

Novel aminopyridazine derivative of minaprine modified by radiolysis presents potent anti-inflammatory effects in LPS-stimulated RAW 264.7 and DH82 macrophage cells

Radiation molecularly transforms naturally occurring products by inducing the methoxylation, hydroxylation, and alkylation of parent compounds, thereby affecting the anti-inflammatory capacities of those compounds. Minaprine (1) modified by ionizing radiation generated the novel hydroxymethylation hydropyridazine (2), and its chemical structure was determined based on NMR and HRESIMS spectra. Compared to the original minaprine, the novel generated product showed a highly enhanced anti-inflammatory capacity inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 and DH82 macrophage cells. In addition, minaprinol (2) effectively inhibited cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) at the protein level and pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10) production in macrophages.

Nitrogen-containing Heterocyclic Derivatives of 1,3-Thiazolidine-2,4- Diones as Dual Anti-inflammatory and Anti-oxidant Agents and their Docking Studies

Aim: The aim of this study was to carry out synthesis and characterization of nitrogencontaining heterocyclic derivatives of 1,3-thiazolidine-2,4-diones as dual anti-inflammatory and antioxidant agents and their docking studies. Background: Inflammation is a protective mechanism of our body to reduce injury and infection by microorganisms. The COX-2 enzyme is responsible for the production of prostaglandins (PG1), which are responsible for pain, fever, and a variety of other inflammatory symptoms. Reactive oxygen species (ROS) are important signalling molecules during inflammatory diseases. In an inflammatory state, polymorphonuclear neutrophils (PMNs) produce oxidative stress, which causes inter-endothelium junctions to open and the transfer of inflammatory cells over the endothelial barrier to increase. Tissue damage is caused by these inflammatory cells. Objective: The objective was to club thiazolidinediones with benzimidazole, triazole, and indole to achieve an enhanced anti-inflammatory effect. Method: In the current report, we have synthesized three new series of indole/ benzimidazole/benzotriazole clubbed with 5-arylidene-2,4-thiazolidinediones. The synthesized compounds were tested for in vivo anti-inflammatory activity using a carrageenan-induced rat paw edema model and in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP) and hydrogen peroxide methods. Result: The results demonstrated that the compound PC-5 exhibited significant anti-inflammatory activity with 61.9% inhibition in comparison to the standard drug diclofenac sodium (71.4% inhibition) after 3h. The compound PC-5 exerted the highest antioxidant activity with an IC50 value of 24.68 μM amongst all synthesized compounds. Acute toxicity was also evaluated for all synthesized compounds, and the results indicated that all evaluated compounds were nontoxic in animals. The replacement of benzotriazole with benzimidazole and indole moieties diminished the anti-inflammatory activity. The hydroxysubstituted arylidene showed higher activity than methoxy, chloro substituted arylidene-2,4- thiazolididiones. Docking studies revealed that the compound PC-5 showed higher inhibition activity against the COX-2 receptor rather than COX-1. The ADME properties were also assessed that showed no violation of Lipinski’s rule and no toxicity. Conclusion: The substituents were found to exert varied activity. The docking studies revealed that the compounds showed lesser binding energy with COX-1 as compared to standard drug diclofenac. Moreover, the binding with COX-2 exhibited more binding energy, thereby proving to have specific COX2 inhibitory activity. All synthesised compounds have shown good antioxidant activity in addition to antiinflammatory activity. PC-5, PC-4, PB-5, PB-4, PA-5, and PA-4 were found to have increased antioxidant activity. Because of the presence of an electron-releasing hydroxyl group, PC-5 has proven to be a highly potent antioxidant agent.

Beneficial Effects of Astragalus membranaceus (Fisch.) Bunge Extract in Controlling Inflammatory Response and Preventing Asthma Features.

Astragalus membranaceus (Fisch.) Bunge root is used as herbal medicine for its immunomodulating activities in Chinese medicine. Recently, beneficial properties of A. membranaceus on allergic diseases have been proposed. Here we investigated the role of a commercial extract of A. membranaceus, standardized to 16% polysaccharides, in regulating the immune-inflammatory response in vitro and in vivo and its therapeutic application in asthma. A. membranaceus extract inhibited prostaglandin E2 and leukotriene C4 production in stimulated J774 and peritoneal macrophages, respectively. The extract also reduced interlukin-1β, tumor necrosis factor-α, and nitrite production, affecting inducible nitric oxide synthase expression. In vivo experiments confirmed the anti-inflammatory properties of A. membranaceus, as evident by a reduction in zymosan-induced peritoneal cellular infiltration and pro-inflammatory mediator production. The efficacy of A. membranaceus extract in modulating the immune response was confirmed in a model of allergic airway inflammation. Extracts improve lung function by inhibiting airway hyperresponsiveness, airway remodeling, and fibrosis. Its anti-asthmatic effects were further sustained by inhibition of the sensitization process, as indicated by a reduction of ovalbumin-induced IgE levels and the mounting of a Th2 immune response. In conclusion, our data demonstrate the anti-inflammatory properties of the commercial extract of A. membranaceus and its beneficial effects on asthma feature development.

Evaluation of salivary Tumor Necrosis Factor-Alpha in patients with hypothyroidism and periodontitis: A Case- Control Study

Introduction: The immune system has served as a bridge among periodontitis and the endocrine system, particularly in the case of thyroid disorders. After non-surgical periodontal therapy for hypothyroid patients, serum thyroid stimulating hormone levels fall within the normal limits, which reduces the inflammatory markers linked to both periodontal and hypothyroid diseases. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), released by macrophages, plays a significant role in bone loss caused by periodontitis. TNF-α will increase the production of collagenases, prostaglandin E2, chemokines and cytokines, cell adhesion molecules, and factors that are related to bone resorption. The aim of our study is to evaluate the salivary level of TNF-α in hypothyroidism patients with periodontitis in comparison to healthy controls.&#x0D; Material and subject: Saliva were collected from 90 subjects with age ranged between (22-65) years, 50 of them hypothyroid patients (25 patients with hypothyroidism and healthy periodontium, 25 patients with hypothyroidism and periodontitis) and 25 patients with periodontitis and systemically healthy compare with 15 subject as control (systemically healthy with healthy periodontium). Detection of TNF-α in saliva was done by using Enzyme Linked Immunosorbent Assay.&#x0D; &#x0D; Result: The current results revealed that salivary TNF-α levels are significantly high (p&lt;0.001) in diseases group (periodontitis group (132.8 ng/L), hypothyroid patients groups without periodontitis (128.4 ng/L) and with periodontitis (117.0 ng/L) as compared to control group (73.4 ng/L), while there are no significant difference between diseases group.&#x0D; Conclusion: Salivary TNF-α level increased significantly in all diseased groups (periodontitis group, hypothyroidism groups with and without periodontitis) in comparison to healthy subject.

Targeting PTGES/PGE2 axis enhances sensitivity of colorectal cancer cells to 5-fluorouracil.

Insensitivity and resistance to 5-fluorouracil (5FU) remain as major hurdles for effective and durable 5FU-based chemotherapy in colorectal cancer (CRC) patients. In this study, we identified prostaglandin E synthase (PTGES)/prostaglandin E2 (PGE2) axis as an important regulator for 5FU sensitivity in CRC cells. We found that PTGES expression and PGE2 production are elevated in CRC cells in comparison to normal colorectal epithelial cells. Depletion of PTGES significantly enhanced the inhibitory effect of 5FU on CRC cell viability that was fully reverted by exogenous supplement of PGE2. Inhibition of PTGES enzymatic function, by either inducing loss-of-function mutant or treatment with selective inhibitors, phenocopied the PTGES depletion in terms of 5FU sensitization. Mechanistically, PTGES/PGE2 axis modulates glycolysis in CRC cells, thereby regulating the 5FU sensitivity. Importantly, high PTGES expression is correlated with poor prognosis in 5FU-treated CRC patients. Thus, our study defines PTGES/PGE2 axis as a novel therapeutic target for enhancing the efficacy of 5FU-based chemotherapy in CRC.

Fucoidan from Sargassum autumnale Inhibits Potential Inflammatory Responses via NF-κB and MAPK Pathway Suppression in Lipopolysaccharide-Induced RAW 264.7 Macrophages.

Fucoidans are sulfate-rich polysaccharides with a wide variety of beneficial biological activities. The present study aimed to highlight the anti-inflammatory activity of fucoidan from the brown seaweed Sargassum autumnale (SA) against lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. Among the isolated fucoidan fractions, the third fraction (SAF3) showed a superior protective effect on LPS-stimulated RAW 264.7 cells. SAF3 inhibits nitric oxide (NO) production and expression of prostaglandin E-2 (PGE2) via downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) expression in LPS-induced RAW 26.7 cells. SAF3 treatment decreased pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 expression in LPS-induced cells. LPS stimulation activated NF-κB and MAPK signaling cascades in RAW 264.7 cells, while treatment with SAF3 suppressed them in a concentration-dependent manner. Existing outcomes confirm that SAF3 from S. autumnale possesses potent anti-inflammatory activity and exhibits good potential for application as a functional food ingredient or for the treatment of inflammation-related disorders.

Preparation and characterization of dummy template molecularly imprinted polymers coupled with HPLC for selective extraction of spiked cloprostenol from milk samples

This study was conducted to develop a particular sorbent for the selective extraction of the luteolytic drug cloprostenol from milk samples. Cloprostenol's luteolytic activity has been proved in animals, whereas the production of prostaglandins is discussed extensively in the literature, while extraction of cloprostenol is rarely discussed. The major objective was to get sufficient molecularly imprinted polymers (MIPs) for selective extraction and detection of cloprostenol. After a series of experiment, MIPs and their analogues NIPs, were synthesized. In these experiments, radical polymerization with non-covalent interactions has been used to synthesize MIPs and NIPs. Different parameters to determine the optimization conditions such as solvent volume, cross-linker, and template ratio were studied in various sets to get better possible characteristics of MIPs. The HPLC was used to evaluate the retention capacity which ranges from 68.5% to 94.1%. The mechanism of adsorption was studied by the isothermal assay and kinetic studies. The kinetic studies exhibited a high retention capacity within 20 min of MIPs contact. The percentage of polymer yield ranged from 53.5% to 92.3%. HPLC coupled with a UV detector showed the limit of detection and limit of quantification of 30.5 ng/mL and 86.7 ng/mL, respectively, for the determination of analytes from milk samples. The recovery of cloprostenol for all spiked samples of milk was higher than 91.54%. Furthermore, the studies showed that MIPs are specific in the adsorption of cloprostenol compared to its other structural analogues. The outcomes also showed the significance of cross-linker concentration and the amount of solvent during the process of polymerization. These parameters greatly affect the preorganization of complementary functional groups, meanwhile, it creates specific cavities for the targeted drugs.

Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets.

Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During Drosophila oogenesis, LD accumulation coincides with the actin remodeling necessary for follicle development. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when the prostaglandin (PG) synthase Pxt is missing. Dominant genetic interactions and PG treatment of follicles indicate that ATGL acts upstream of Pxt to regulate actin remodeling. Our data suggest that ATGL releases arachidonic acid (AA) from LDs to serve as the substrate for PG synthesis. Lipidomic analysis detects AA-containing triglycerides in ovaries, and these are increased when ATGL is lost. High levels of exogenous AA block follicle development; this is enhanced by impairing LD formation and suppressed by reducing ATGL. Together, these data support the model that AA stored in LD triglycerides is released by ATGL to drive the production of PGs, which promote the actin remodeling necessary for follicle development. We speculate that this pathway is conserved across organisms to regulate oocyte development and promote fertility.

The Anti-Inflammatory Effect of Low Molecular Weight Fucoidan from Sargassum siliquastrum in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages via Inhibiting NF-κB/MAPK Signaling Pathways.

Brown seaweed is a rich source of fucoidan, which exhibits a variety of biological activities. The present study discloses the protective effect of low molecular weight fucoidan (FSSQ) isolated from an edible brown alga, Sargassum siliquastrum, on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW 264.7 macrophages. The findings of the study revealed that FSSQ increases cell viability while decreasing intracellular reactive oxygen species production in LPS-stimulated RAW 264.7 macrophages dose-dependently. FSSQ reduced the iNOS and COX-2 expression, inhibiting the NO and prostaglandin E2 production. Furthermore, mRNA expression of IL-1β, IL-6, and TNF-α was downregulated by FSSQ via modulating MAPK and NF-κB signaling. The NLRP3 inflammasome protein complex, including NLRP3, ASC, and caspase-1, as well as the subsequent release of pro-inflammatory cytokines, such as IL-1β and IL-18, release in LPS-stimulated RAW 264.7 macrophages was inhibited by FSSQ. The cytoprotective effect of FSSQ is indicated via Nrf2/HO-1 signaling activation, which is considerably reduced upon suppression of HO-1 activity by ZnPP. Collectively, the study revealed the therapeutic potential of FSSQ against inflammatory responses in LPS-stimulated RAW 264.7 macrophages. Moreover, the study suggests further investigations on commercially viable methods for fucoidan isolation.

Global gene expression in equine endometrium around the time of maternal recognition of pregnancy

The conceptus-maternal communication during the preimplantation period, also known as maternal recognition of pregnancy (MRP), is crucial for the establishment and maintenance of pregnancy. This communication affects the endometrial transcriptome and proteome with subsequent reduction of endometrial pulsatile prostaglandin F2α secretion and the consequent extension of the corpus luteum's lifespan during early pregnancy in the mare. Also, this communication results in the preparation of the uterine environment for implantation. Any alteration of these processes will result in early embryonic death. Therefore, a better understanding of the normal endometrial transcriptomic changes around the time of MRP might be the key to understanding and preventing early embryonic loss. This study aimed to evaluate the endometrial transcriptome from Day 14 (Day 0 = ovulation) of pregnant and non-pregnant (i.e. diestrus) mares. RNA was isolated from pregnant (n=5) and non-pregnant (n=4) endometrial tissue samples. RNA-Seq was performed using Illumina NovaSeq6000 and differentially expressed genes (DEGs) were evaluated using DESeq.2 based upon an FDR<0.05. Our study identified 1193 DEGs (570 upregulated DEGs and 623 downregulated DEGs) in the pregnant endometrium as compared to the non-pregnant endometrium. In the current study, the pregnant endometrium was associated with downregulation (9.6-fold change) of mRNA forprostaglandin-endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2 enzyme; COX2), which encodes for the rate-limiting enzyme in prostaglandin production. Gene ontology analysis of DEGs revealed that these genes were associated with relevant biological processes such as immune response (TNFAIP1, TNF, CXCR2, TNFSF15, IL15, TGFBR3, IL1B, TNFSF9, TLR8), regulation of trophoblast cell proliferation and migration (BOK, LIF, RBM46, TIMP1, CALR, GJA1), embryo growth and development (PTCH1, PTCH2R, DH10, GLI3, SHOX2, ZDBF2, EVX1, GREM2, KLF2, TWIST1), cell adhesion (COL28A1, EGFL6, ITGA3, FN1, NEDD9, LAMC2, RGMB, THBS4, RHOB, SELP, CHL1, CDHR1, MXRA8, FOLR3, NECTIN3), embryo implantation (MMP9 and LIF), placenta development (ADAM19, MAPK14, BIRC3), amino acids transportation (SLC1A1, SLC25A29, SLC36A2, SLC38A2, SLC7A5), steroid biosynthesis and metabolism (SRD5A1, HSD11B2, HSD17B7, CYP20A1), and progesterone receptors (PAQR5, and PGRMC1). Several of the DEGs identified in the current study are known to play a role in controlling endometrial receptivity to the conceptus in species other than the equine. These findings improve our understanding of the molecular changes taking place in equine endometrium around the time of MRP which might help us to understand and forestall early embryonic loss in the future.