Serum Prostaglandin E2 Levels Research Articles

Unveiling the Potency of Gardenia Extract Against H. pylori: Insights from In Vitro and In Vivo Studies.

Gardenia jasminoides (G. jasminoides) could treat various inflammatory diseases. This study aimed to investigate the effects of G. jasminoides fruit extract on gastric inflammation and protective mechanisms in Helicobacter pylori (H. pylori)-induced gastritis. Experimental procedure: G. jasminoides fruit extract was prepared and analyzed for geniposide content. The inhibitory effect of the extract on H. pylori growth was investigated using the disk diffusion method. The in vitro anti-inflammatory property of the extract was evaluated using the erythrocyte membrane stabilization method. Thirty-five male Sprague-Dawley rats were inoculated with H. pylori (108-1010 colony-forming unit/mL) and divided into five groups. Each group was treated with various doses of the extract (98-395 mg/kg). The serum and stomach tissue of the rats were evaluated using enzyme-linked immunosorbent assay, histopathology, and immunohistochemistry. The geniposide content in the dried extract was 8.12% ± 0.79% by dry weight. The inhibition zone was observed at the extract ≥ 1.97 mg/disk, and the extract presented anti-inflammatory potential. The H. pylori-inoculated rats had a significant increase in serum interleukin (IL)-17, IL-33, and gastric epidermal growth factor (EGF) levels and a significant decrease in serum prostaglandin E2 level (p < 0.05) in conjunction with the development of gastric inflammation on histopathology. The treatment of the extract could significantly decrease the serum IL-17, IL-33, and gastric EGF levels, significantly increase the serum PGE2 level (p < 0.05), and improve gastric histopathology. Thus, G. jasminoides fruit extract attenuated H. pylori-induced gastritis by inhibiting bacterial growth, reducing inflammation, and enhancing protective mechanisms.

Salmon Nasal Cartilage-Derived Proteoglycans Alleviate Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

Osteoarthritis is a chronic inflammatory condition characterized by the degeneration of joint cartilage and underlying bone, resulting in pain, swelling, and reduced mobility. This study evaluates the efficacy of salmon nasal cartilage-derived proteoglycans in mitigating osteoarthritis symptoms and investigates the underlying molecular mechanisms. This study employed a rat model of osteoarthritis induced by monosodium iodoacetate (MIA) injection. The rats were orally administered salmon nasal cartilage-derived proteoglycans or ibuprofen. Key aspects of osteoarthritis pathology, including impaired exercise ability, inflammation, extracellular matrix degradation, and chondrocyte apoptosis, were assessed using histological analysis, micro-CT, treadmill testing, serum assays, and mRNA/protein expression studies. The MIA injection caused significant cartilage damage, reduced bone mineral density, and impaired exercise ability. Additionally, it elevated serum levels of prostaglandin E2 and nitric oxide, increased the mRNA and protein levels of inflammation-related factors, and activated apoptosis signaling pathways in cartilage. Treatment with salmon nasal cartilage-derived proteoglycans significantly improved cartilage morphology and mineralization, reduced inflammation, and inhibited apoptosis signaling pathways, with effects comparable to those observed with ibuprofen treatment. These findings highlight the potential of salmon nasal cartilage-derived proteoglycans as a therapeutic agent for managing osteoarthritis by effectively reducing inflammation, preventing cartilage degradation, and inhibiting chondrocyte apoptosis.

Ellagic acid improves osteoarthritis by inhibiting PGE2 production in M1 macrophages via targeting PTGS2.

Osteoarthritis (OA) is a degenerative joint disease characterised by inflammation and cartilage degeneration. Ellagic acid (EA) might have therapeutic potential in OA, but its molecular mechanisms of action remain unclear. In this study, we aimed to identify the docking protein of EA in M1 macrophage-related pro-inflammation in OA. Bioinformatics analysis was performed to identify ellagic acid's potential targets among OA-related dysregulated genes. THP-1 cells were induced into M0 and polarised into M1 macrophages for in vitro studies. Mice knee models of OA were generated for in vivo studies. Results showed that PTGS2 (also known as COX-2) is a potential target of ellagic acid among OA-related dysregulated genes. EA has multiple low-energy binding sites on PTGS2, including sites containing amino acid residues critical for the enzyme's catalytic activity. Surface plasmon resonance (SPR) assays confirmed the physical interaction between ellagic acid and recombinant PTGS2 protein, with a dissociation constant (KD) of 5.03 ± 0.84 μM. EA treatment suppressed PTGS2 expression and prostaglandin E2 (PGE2) production in M1 macrophages. Besides, ellagic acid can directly inhibit PTGS2 enzyme activity, with an IC50 around 50 μM. Importantly, in a mouse model of OA, ellagic acid administration alleviated disease severity, reduced collagen II degradation and MMP13 generation, and decreased serum PGE2 levels. Collectively, these results suggest that PTGS2 is a key target of ellagic acid's anti-inflammatory and chondroprotective effects in OA.

The importance of mechanosensitive cell mediated prostaglandin and nitric oxide synthesis in the pathogenesis of apical periodontitis: comparative with chronic periodontitis

ObjectivesMechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as prostaglandin E2 (PGE2) and nitric oxide (NO) as an adaptive response. It is thought that these synthesized molecules can be used for the diagnosis and treatment of periodontal and periapical diseases. The aim of this study was to investigate the relationship between the severity of apical periodontitis (AP) and chronic periodontitis (CP) and serum (s) TNF-α, IL-10, PGE2 and NO levels, as well as PGE2 and NO levels in gingival crevicular fluid (GCF) samples.Materials & methodsA total of 185 subjects were divided into three categories: AP group (n = 85), CP group (n = 50) and healthy control group (n = 50). The AP group was divided into 3 subgroups according to abscess scoring (AS-PAI 1, 2 and 3) based on the periapical index. The CP group was divided into 4 subgroups according to the periodontitis staging system (PSS1, 2,3 and 4). After recording the demographic and clinical characteristics of all participants, serum (s) and gingival crevicular fluid (GCF) samples were taken. TNF-α, IL-10, PGE2 and NO levels were measured in these samples.ResultsUnlike serum measurements (sTNF-α, sIL-10, sNO and sPGE2), GCF-NO and GCF-PGE levels of the AP group were significantly higher than the control group in relation to abscess formation (54.4 ± 56.3 vs. 22.5 ± 12.6 µmol/mL, p < 0.001 and 100 ± 98 vs. 41 ± 28 ng/L, p < 0.001, respectively). Confirming this, the GCF-NO and GCF-PGE levels of the AS-PAI 1 group, in which abscesses have not yet formed, were found to be lower than those in AS-PAI 2 and 3, which are characterized by abscess formation [(16.7(3.7-117.8), 32.9(11.8-212.8) and 36.9(4.3-251.6) µmol/mL, p = 0,0131; 46.0(31.4–120.0), 69.6(40.3-424.2) and 74.4(32.1–471.0) ng/L, p = 0,0020, respectively]. Consistent with the increase in PSS, the levels of sTNF [29.8 (8.2-105.5) vs. 16.7(6.3–37.9) pg/mL, p < 0.001], sIL-10 [542(106–1326) vs. 190(69–411) pg/mL, p < 0.001], sNO [182.1(36.3–437) vs. 57.0(15.9–196) µmol/mL, p < 0.001], sPGE2 [344(82-1298) vs. 100(35-1178) ng/L, p < 0.001], GCF-NO [58.9 ± 33.6 vs. 22.5 ± 12.6 ng/L, p < 0.001] and GCF-PGE2 [ 99(37–365) vs. 30(13–119), p < 0.001] in the CP group were higher than the control group. Comparison ROC analysis revealed that the GCF-PGE2 test had the best diagnostic value for both AP and CP (sensitivity: 94.1 and 88.0; specificity: 64.0 and 78.0, respectively; p < 0.001).ConclusionsGCF-PE2 and GCF-NO have high diagnostic value in the determination of AP and CP, and can be selected as targets to guide treatment. In addition, the measurements of PGE2 and NO in GCF can be used as an important predictor of pulpal necrosis leading to abscess in patients with AP.Clinical relevanceIn this article, it is reported that syntheses of early signaling molecules such as PGE2 and NO can be used for the diagnosis and treatment target of periapical and periodontal infections.

Contribution of non-steroidal anti-inflammatory drugs to breast cancer treatment: In vitro and in vivo studies.

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.

Maternal supplementation with docosahexaenoic acid does not cause constriction of fetal ductus arteriosus: randomized controlled trial.

Docosahexaenoic acid (DHA) is recommended routinely in pregnancy to promote fetal development. DHA has anti-inflammatory activity, but its effects on the fetal heart and circulation are unknown. This study aimed to investigate whether maternal DHA supplementation in the third trimester affects maternal prostaglandin levels and fetal ductus arteriosus flow dynamics. This was a double-blind randomized controlled trial with parallel groups conducted between 2018 and 2021. Pregnant women aged over 18 years with a normal fetus at 27-28 weeks' gestation showing no cardiac/extracardiac anomalies or ductal constriction were eligible for the trial. Women consuming substances with a known inhibitory effect on prostaglandin metabolism, such as non-steroidal anti-inflammatory drugs and polyphenol-rich foods, were excluded. The intervention group received oral supplementation of omega-3 with 450 mg/day of DHA for 8 weeks and the placebo group received capsules of soy lecithin for 8 weeks. Anthropometric measurements, assessment of polyphenol and omega-3 consumption, fetal morphological ultrasound examination, fetal Doppler echocardiographic examination and blood sample collection were performed at the start of the study and the latter two were repeated at follow-up. Prostaglandin E2 (PGE2) level and echocardiographic parameters were compared between the intervention and placebo groups and between baseline and follow-up. A total of 24 participants were included in each group. After 8 weeks, there were no significant differences between the intervention and placebo groups in maternal serum PGE2 level or Doppler echocardiographic parameters of ductal flow. No case of ductus arteriosus constriction was observed. The expected intragroup changes in cardiac morphology, as a result of advancing gestation, were present. Maternal DHA supplementation in the third trimester at a clinically recommended dose did not result in inhibition of PGE2 or constriction of the ductus arteriosus. These findings should be confirmed in postmarket surveillance studies with larger patient numbers in order to test the full safety profile of DHA and provide robust clinical reassurance. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Ge-gen decoction alleviates primary dysmenorrhoea symptoms in a rat model

Background Existing treatments for primary dysmenorrhoea (PD), such as NSAIDs, impart side effects. Ge-Gen decoction (GGD), a traditional Chinese medicine, has shown promise in treating PD, but its exact mechanisms remain unclear. Here, we aimed to investigate the efficiency of GGD in alleviating PD using a rat model to understand its precise mechanism of action. Methods We established a rat model of dysmenorrhoea induced by oestradiol and oxytocin. The PD rats were administered GGD or Ibuprofen (positive control) intragastrically once daily for seven consecutive days. Serum levels of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), β-endorphin (β-EP), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression levels of oestrogen receptor alpha (ERα) and cyclooxygenase-2 (COX-2) in uterine tissue were measured using immunohistochemical assays, and those of phosphorylated and total extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) were assessed using western blot analysis. Results Treatment with GGD significantly reduced writhing behaviour, histopathological scores, and levels of COX-2, PGE2, and PGF2α in the serum of PD rats. Additionally, GGD increased β-EP content and inhibited ERK1/2 activation and ERα expression in uterine tissues. Conclusions The results of this study suggest that GGD alleviates PD in rats by suppressing the COX-2-mediated release of PGE2 and PGF2α, modulating the ERα/ERK1/2/COX-2 pathway, and increasing β-EP content. These results provide insights into the potential mechanisms of GGD in treating PD and support its further investigation as an alternative therapy for this condition.

Exploring PGE2 and LXA4 Levels in Migraine Patients: The Potential of LXA4-Based Therapies.

Neurogenic inflammation plays a significant role in the pathogenesis of migraines. This study aimed to investigate the serum levels of prostaglandin E2 (PGE2), lipoxin A4 (LXA4), and other inflammatory biomarkers (C-reactive protein, fibrinogen) in migraine patients. In total, 53 migraine patients and 53 healthy controls were evaluated. Blood serum samples were collected during both attack and interictal periods and compared with the control group. In both the attack and interictal periods, PGE2 and LXA4 values were significantly lower in migraine patients compared to the control group (p < 0.001). Additionally, PGE2 values during the attack period were significantly higher than those during the interictal period (p = 0.016). Patients experiencing migraine attacks lasting ≥ 12 h had significantly lower serum PGE2 and LXA4 levels compared to those with attacks lasting < 12 h (p = 0.028 and p = 0.009, respectively). In ROC analysis, cut-off values of 332.7 pg/mL for PGE2 and 27.2 ng/mL for LXA4 were determined with 70-80% sensitivity and specificity. In conclusion, PGE2 and LXA4 levels are significantly lower in migraine patients during both interictal and attack periods. Additionally, the levels of LXA4 and PGE2 decrease more with the prolongation of migraine attack duration. Our findings provide a basis for future treatment planning.

Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis.

This study aimed to investigate the changes of serum carbohydrate antigen 125 (CA125) and prostaglandin E2 (PGE2) in patients with adenomyosis before and after treatment with high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist (GnRH-a). One hundred and sixty-five patients with adenomyosis who received HIFU combined with GnRH-a were selected as case group. Sixty-five healthy women who underwent physical examination at the same time were taken as normal control group. At the end of follow-up 6 months after treatment, the case group were divided into effective subgroup and ineffective subgroup according to clinical efficacy. Changes of serum CA125 and PGE2 were analyzed. Serum CA125 and PGE2 levels in the case group were higher than those in the normal control group before treatment (both P < 0.001). Serum CA125 and PGE2 levels in the case group 6 months after treatment were lower than those before treatment (both P < 0.001). There was no difference in serum CA125 and PGE2 levels between effective subgroup and ineffective subgroup before treatment (P = 0.351, 0.284, respectively). Serum CA125 and PGE2 levels in the effective subgroup were lower than those in the ineffective subgroup 6 months after treatment (both P < 0.001). Serum CA125 and PGE2 may be involved in the development of adenomyosis, and their expression levels may be related to the prognosis of patients. Levels of serum CA125 and PGE2 in patients with adenomyosis decrease after treatment with HIFU combined with GnRH-a. The detection of serum CA125 and PGE2 may be used as an index to diagnose adenomyosis and evaluate the therapeutic effect of HIFU combined with GnRH-a.

Melanoxetin: A Hydroxylated Flavonoid Attenuates Oxidative Stress and Modulates Insulin Resistance and Glycation Pathways in an Animal Model of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin's therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

Eichhornia crassipes Ameliorated Rheumatoid Arthritis by Modulating Inflammatory Cytokines and Metalloproteinase Enzymes in a Rat Model.

Background and Objectives: This study was planned to investigate the anti-arthritic property of flowers of E. crassipes in a Sprague-Dawley rat model by administering Freund's Complete Adjuvant (FCA). Materials and Methods: Arthritis was induced at day 0 in all rats except negative controls, while arthritic progress and paw edema were analyzed on specific days (8th, 13th, 18th, and 23rd) via the macroscopic arthritic scale and a digital Vernier caliper, respectively. Histopathological parameters were examined using a Hematoxylin and Eosin (H&E) staining method. Blood samples were withdrawn from rats to investigate the effects of the E. crassipes flower on the mRNA expression values of inflammatory markers, via a reverse transcription PCR technique. Serum samples were used to determine prostaglandin E2 (PGE2) levels using enzyme-linked immunosorbent assay (ELISA). Values of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine, and urea, besides hematological parameters, i.e., the hemoglobin (Hb) content and complete blood count (CBC), were investigated. Results: The data showed that E. crassipes inhibited the arthritic progress and ameliorated the paw edema. The amelioration of parameters assessed via the histopathological analysis of ankle joints, as well as via hematological analysis, confirmed the diminution of rheumatoid arthritis (RA) in the plant-treated groups. Treatment with E. crassipes inhibited the expression levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6), nuclear factor KappaB (NF-κB), matrix metalloproteinase (MMP-2 and MMP-3), and vascular endothelial growth factor (VEGF). Serum PGE2 levels were also found to be reduced in treatment groups. A biochemical investigation revealed the improvements in hepatic markers in plant-treated groups. The data indicated that the plant has no hepatotoxic or nephrotoxic effects at the studied dose. GC-MS (Gas Chromatography-Mass Spectrometry) analysis displayed the presence of phytochemicals having known anti-inflammatory and antioxidant properties. Conclusions: Therefore, it may be concluded that E. crassipes possesses anti-arthritic characteristics that could be attributed to the modulation of pro-inflammatory cytokines, MMPs, and PGE2 levels.

Effects of Vitamin A on Immune Responses and Vitamin A Metabolism in Broiler Chickens Challenged with Necrotic Enteritis.

Necrotic enteritis (NE) is an important enteric inflammatory disease of poultry, and the effects of vitamin A (VitA) on NE birds are largely unknown. The present study was conducted to investigate the effects of VitA on the immune responses and VitA metabolism of NE broilers as well as the underlying mechanisms. Using a 2 × 2 factorial arrangement, 336 1-day-old Ross 308 broiler chicks were randomly assigned to 4 groups with 7 replicates. Broilers in the control (Ctrl) group were fed a basal diet without extra VitA supplementation. Broilers in the VitA group were fed a basal diet supplemented with 12,000 IU/kg of VitA. Birds in NE and VitA + NE groups were fed corresponding diets and, in addition, co-infected with Eimeria spp. and Clostridium perfringens on days 14 to 20. Samples of the blood, jejunum, spleen and liver were obtained on day 28 for analysis, and meanwhile, lesion scores were also recorded. The results showed that NE challenge increased lesion score in the jejunum and decreased serum glucose, total glyceride, calcium, phosphorus and uric acid levels (p < 0.05). VitA supplementation reduced the levels of serum phosphorus, uric acid and alkaline phosphatase in NE-challenged birds and increased serum low-density lipoprotein content and the activity of aspartate aminotransferase and creatine kinase (p < 0.05). Compared with the Ctrl group, the VitA and NE groups had higher mRNA expression of interferon-γ in the jejunum (p < 0.05). NE challenge up-regulated mRNA expression of interleukin (IL)-13, transforming growth factor-β4, aldehyde dehydrogenase (RALDH)-2 and RALDH-3 in the jejunum, while VitA supplementation increased jejunal IL-13 mRNA expression and hepatic VitA content, but down-regulated splenic IL-13 mRNA expression (p < 0.05). The VitA + NE group had higher serum prostaglandin E2 levels and the Ctrl group had higher splenic RALDH-3 mRNA expression than that of the other three groups (p < 0.05). NE challenge up-regulated jejunal retinoic acid receptor (RAR)-β and retinoid X receptor (RXR)-α as well as splenic RAR-α and RAR-β mRNA expression (p < 0.05). VitA supplementation up-regulated jejunal RAR-β expression but down-regulated mRNA expression of RXR-α, RXR-γ, signal transducers and activators of transcription (STAT) 5 and STAT6 in the spleen (p < 0.05). Moreover, compared with the Ctrl group, the VitA and NE groups had down-regulated mRNA expression of jejunal and splenic Janus kinase (JAK) 1 (p < 0.05). In conclusion, NE challenge induced jejunal injury and expression of Th2 and Treg cell-related cytokines and enhanced RALDH and RAR/RXR mRNA expression, mainly in the jejunum of broilers. VitA supplementation did not alleviate jejunal injury or Th2 cell-related cytokine expression; however, it improved hepatic VitA deposition and inhibited the expression of RALDH-3, RXR and the JAK/STAT signaling pathway in the spleen of broilers. In short, the present study suggested the modulatory effects of vitamin A on the immune responses and vitamin A metabolism in broiler chickens challenged with necrotic enteritis.

Effect of Electroacupuncture on NLRP3 Inflammasome and Morphology of Uterine in Rats with Primary Dysmenorrhea Based on Meridian Acupoint Viscera Correlation Theory

Objective: To explore the relationship between acupoints and the uterus in primary dysmenorrhea (PDM) and observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and morphology of uterine tissues in rats. Materials and Methods: Rats were divided into four groups: Control, PDM, EA, and nonacupoint EA (sham) groups. Writhing reactions in the rats were carefully monitored. Prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) levels in the rat serum were measured using the enzyme-linked immunosorbent assay. To assess the damage, the histomorphology of the rat uterus was examined using the optical and electron microscopy. Western blotting was performed to determine the nucleotide-binding oligomerization domain carboxy-terminal leucine-rich repeat domain and amino-terminal pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC), and cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1β (IL-1β), and IL-18. Results: Compared with the control group, the PDM group exhibited significant increases in both writhing times and scores, with a high pathological score of the uterine tissue. Serum PGF2α levels were significantly elevated, whereas PGE2 levels were significantly reduced. In addition, the expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 significantly increased (P &lt; 0.001). The EA group showed opposite effects from the PDM group (all P &lt; 0.05). The sham group exhibited significantly higher writhing time, serum PGF2α levels, and expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 than the EA group. In contrast, serum PGE2 levels in the sham group were significantly lower than those in the EA group (all P &lt; 0.05). Conclusions: NLRP3 inflammasome activation in PDM triggers pathological inflammation. Sanyinjiao(SP6) and Guanyuan(CV4) had specific effects on PDM. EA of SP6 and CV4 may treat PDM by inhibiting inflammation and protecting the morphological structure of the uterus.

Effects of electroacupuncture on NLRP3 inflammasome and pyroptosis protein GSDMD in uterine tissue in rats with primary dysmenorrhea

To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM. Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1β, IL-18) in uterine tissue. In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05). EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.

Effects of dietary arachidonic acid supplementation in high plant protein diets on growth, feed utilization, and immunity of olive flounder, Paralichthys olivaceus

This study was designed to evaluate the effects of graded levels of arachidonic acid (ARA) in low fish meal diets (30% fish meal, 30% plant protein blends) on growth, feed utilization, and immunity of olive flounder (Paralichthys olivaceus). The control diet was formulated with 3% fish oil and 5.1% soybean oil (ARA0.0). Five other diets were formulated incorporating different levels of ARA into the ARA0.0 diet at the expense of soybean oil; that is, 0.3, 0.6, 0.9, 1.2, and 1.5% ARA (ARA0.3, ARA0.6, ARA0.9, ARA1.2, and ARA1.5), respectively. Three replicate groups of fish (88.24 ± 0.06 g) were placed into 18 polyvinyl circular tanks (215 L), with 24 fish each and fed an experimental diet twice a day for nine weeks. Overall, significantly improved growth performance was observed in the ARA0.6 group. Liver C18:2n-6 was significantly reduced, and liver ARA content was significantly increased with the increase in dietary ARA levels. Nitroblue tetrazolium activity was significantly higher in the ARA0.6 group, and significantly higher superoxide dismutase and myeloperoxidase activities were observed in the ARA0.9 group. Further, immunoglobulin level and lysozyme activity were significantly improved in the ARA0.3 group, antiprotease activity was increased in the ARA0.6 and ARA0.9 groups, and the ARA0.3 group showed lower liver lipid content than the ARA0.0 group. Serum prostaglandin E2 level was significantly increased with 1.5% ARA inclusion. Pro-inflammatory gene expressions of interleukin (IL)-6, IL-8, IL-10, perforin, and tumor necrosis factor in the intestine were significantly downregulated, and anti-inflammatory gene expression of transforming growth factor-β2 gene expression was significantly upregulated with higher dietary ARA supplementation (0.9–1.5%). These results indicate that 0.3–0.9% supplemented ARA may improve the growth, immune, and hematological parameters of olive flounder.

Clinical effect of Anwei Qingyou recipe on peptic ulcer and its effect on the levels of EGF and PGE2: A retrospective study.

Background:To investigate the effect of Anwei Qingyou formula on the clinical treatment of patients with peptic ulcer (PU) and its effect on the levels of epidermal growth factor (EGF) and prostaglandin E2 (PGE2).Methodology:Medical records of 83 patients with PU, treated in our hospital from January 2020 to January 2021, were retrospectively analyzed. Among them, 40 patients received conventional triple therapy (scheme I), that is, oral omeprazole, clarithromycin and amoxicillin, twice a day, and 43 patients received conventional triple therapy + Anwei Qingyou formula, taken orally twice a day (scheme II). The improvement of clinical symptoms, the quality of ulcer healing, clinical effectiveness and recurrence rate were analyzed after 4 weeks of treatment. Patients were followed up for six months.Results:After treatment with corresponding regimen, the total clinical effective rate of scheme II was 97.57% (42/43), which was significantly higher than 82.50% (33/40) of scheme I. Six-month follow-up results showed that the recurrence rate in scheme II patients was 4.65% (2/43), which was significantly lower than 20.00% (8/40) in the scheme I group (χ 2 = 5.479, 4.607, all P < .05). After one course of treatment, the levels of serum EGF and PGE2 in scheme II group were higher than those in scheme I group (P < .05).Conclusion:In combination with the conventional western medicine treatment, Anwei Qingyou formula administration in PU patients effectively improves the overall control of the disease and therapeutic effectiveness.

Higher serum PGE2 is a predicative biomarker for postoperative delirium following elective orthopedic surgery in elderly patients

BackgroundPostoperative delirium (POD), one of the most common complications following major surgery, imposes a heavy burden on patients and society. The objective of this exploratory study was to conduct a secondary analysis to identify whether there exist novel and reliable serum biomarkers for the prediction of POD.MethodsA total of 131 adult patients (≥ 65 years) undergoing lower extremity orthopedic surgery with were enrolled in this study. Cognitive function was assessed preoperatively with Mini-Mental State Examination (MMSE). Delirium was diagnosed according to the Confusion Assessment Method (CAM) criteria on preoperative day and postoperative days 1–3. The preoperative serum levels of a panel of 16 biochemical parameters were measured by ELISA.ResultsThirty-five patients developed POD, with an incidence of 26.7%. Patients in POD group were older (P = 0.001) and had lower preoperative MMSE scores (P = 0.001). Preoperative serum levels of prostaglandin E2 (PGE2, P < 0.001), S100β (P < 0.001), glial fibrillary acidic protein (P < 0.001) and neurofilament light (P = 0.002) in POD group were significantly increased. Logistic regression analysis showed that advanced age (OR = 1.144, 95%CI: 1.008 ~ 1.298, P = 0.037), higher serum neurofilament light (OR = 1.003, 95%CI: 1.000 ~ 1.005, P = 0.036) and PGE2 (OR = 1.031, 95%CI: 1.018 ~ 1.044, P < 0.001) levels were associated with the development of POD. In addition, serum level of PGE2 yielded an area under the ROC curve (AUC) of 0.897 to predict POD (P < 0.001), with a sensitivity of 80% and a specificity of 83.3%.ConclusionsOur study showed that higher preoperative serum PGE2 level might be a biomarker to predict the occurrence of POD in elderly patients undergoing elective orthopedic surgery.Trial registrationNCT03792373 www.clinicaltrials.gov.

Huayu Sanjie Enema Liquid Relieves Pain in Endometriosis Model Rats by Inhibiting Inflammation, Peripheral Sensitization, and Pelvic Adhesion.

The objective of this study is to observe the effect of relieving pain of Huayu Sanjie enema liquid (HYSJ-EL) on endometriosis model rats and to explore its mechanism of action. Of 24 female Sprague Dawley rats, six were randomly selected as the sham operation group (normal control group). The remaining rats were used to establish rat models of endometriosis through autologous endometrial transplantation combined with estrogen injection. Successfully modeled rats were randomly divided into the model, indomethacin (Western medicine group), and HYSJ-EL (Chinese herbs group) treatment groups. The thermal pain threshold of rats was measured, and hematoxylin and eosin staining was used to observe pathological changes after sampling. Serum levels of prostaglandin E2 (PGE2), interleukin-6 (IL-6), macrophage inflammatory protein-2 (MIP-2), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-β (TGF-β) were measured using an enzyme-linked immunosorbent assay (ELISA). Furthermore, the protein and mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1) and tumor necrosis factor-α (TNF-α) in the endometrium and endometriotic lesions were measured using Western blotting and quantitative real-time PCR assays, respectively. Compared to the model group, the heat pain threshold of rats in the HYSJ-EL group was significantly increased (P < 0.01), and the serum levels of PGE2, IL-6, MIP-2, PAI-1, and TGF-β were significantly decreased (P < 0.01), as well as the expression of TRPV1 and TNF-α protein and mRNA in the tissue of the ectopic lesion was significantly decreased (P < 0.05). These results indicate that the Huayu Sanjie enema liquid exerts analgesic effects on endometriosis by inhibiting inflammation, peripheral nerve sensitization, and pelvic adhesion.

Gastro-Protective Effect of Fermented Soybean (Glycine max (L.) Merr.) in a Rat Model of Ethanol/HCl-Induced Gastric Injury.

The present research purposed to examine the gastro-protective effect of Glycine max (L.) Merr. fermented using Lactobacillus delbrueckii ssp. delbrueckii Rosell-187 (Gastro-AD®) on ethanol/HCl-induced gastric damage, specifically on gastric acid secretion. After oral supplementation of Gastro-AD® to Sprague–Dawley (SD) rats with ethanol/HCl-induced gastric damage, we determined that Gastro-AD® attenuated the gastric mucosal lesion, hemorrhage and gastric acid secretion induced by ethanol/HCl. In addition, we observed that the Gastro-AD® treatment increased the serum prostaglandin E2 level and decreased the levels of gastric acid secretion-related receptors in both gastric tissues and primary gastric parietal cells. Furthermore, it decreased the levels of inflammatory factors, including serum histamine and expression of p-IκB, p-p65, iNOS and COX-2 and the activity of apoptotic signaling pathways, including those involving p-JNK, Bcl2/Bax, Fas, FADD, caspase-8 and caspase-3, in the stomach of the ethanol/HCl-treated rats. Thus, we suggest that Gastro-AD® supplementation may reduce ethanol/HCl-induced gastric acid secretion and prevent gastric injury.

Caralluma tuberculata exhibits analgesic and anti-arthritic potential by downregulating pro-inflammatory cytokines and attenuating oxidative stress.

Caralluma tuberculata N.E. Brown (Common name: Chongan), belonging to the family Asclepiadaceae is distributed widely in hilly areas of Dir, Swat, Kohat and in plain lands of Punjab, Pakistan. The plant has been used as a source of vegetable as well as home remedy for headache, muscle spasms and rheumatism. The present study was proposed to investigate the analgesic, anti-inflammatory and anti-arthritic potential of the aqueous methanolic extract of C. tuberculata (ICE). The dried shoots of plant were used to prepare aqueous methanolic extract (30:70) by 3days thrice maceration and filtration followed by evaporation under reduced pressure. ICE was screened for the presence of phytochemicals using preliminary phytochemical analysis and HPLC. The antioxidant potential was evaluated through DPPH assay. Analgesic potential of ICE was studied using hot plate and tail immersion methods, and anti-inflammatory activity was performed using turpentine oil and carrageenan-induced inflammation models, in wistar albino rats. Formaldehyde-induced and Complete Freund's Adjuvant-induced arthritis models were used for the assessment of anti-arthritic activity of ICE and its effects on serum levels of PGE-2 as well as gene expression levels of pro-inflammatory cytokines were studied. ICE displayed a dose-dependent (300-1000mg/Kg p.o.) analgesic effect in hot plate (maximum retention time of 10.87 and 13s) and tail immersion (response time of 11 and 13.64s) tests at the doses of 500 and 1000mg/Kg, respectively. The extract exhibited a significant decrease in paw inflammation of rats at the doses of 500 and 1000mg/Kg as compared to the disease control group. ICE also exhibited a remarkable decline in arthritic score and a dose-dependent drop in serum levels of prostaglandin E2. There was a significant suppression in the expression of TNF-α, IL-1β, IL-6, NF-κB and cyclooxygenase enzyme in treatment groups. This study concludes that Caralluma tuberculata exhibits strong analgesic, anti-inflammatory, antioxidant and anti-arthritic activities thus upholding the vernacular use of the plant for pain and rheumatism.