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OBJECTIVE To study the mechanism of oxymatrine inducing apoptosis of osteosarcoma MG63 cell line based on mitophagy mediated by cyclooxygenase-2 （COX-2）/PTEN-induced putative kinase-1 （PINK1）/Parkinson disease protein-2 （Parkin） signaling pathway. METHODS MG63 cells were treated with 2.0， 4.0， 8.0 mg/mL oxymatrine and 6 μmol/L 5-fluorouracil， then the apoptotic rate， the expression of apoptosis-related proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax）]， the proportion of decrease in mitochondrial membrane potential， the level of mitophagy as well as the protein expressions of PINK1， Parkin， and microtubule-associated protein 1 light chain-3Ⅱ （LC3-Ⅱ） were detected. PINK1 small interfering RNA （siRNA） was adopted to intervene in the expression of PINK1， the cells were divided into control group， PINK1 siRNA group， oxymatrine group， and PINK1 siRNA+oxymatrine group； the protein expressions of PINK1， Parkin， and LC3-Ⅱ， the proportion of decrease in mitochondrial membrane potential （MMP） as well as apoptotic rate were detected. The lentivirus infection technique was used to overexpress COX-2， the cells were divided into control group， oxymatrine group， COX-2 group， and COX-2+oxymatrine group. The protein expressions of COX-2， PINK1， and Parkin， as well as the proportion of decrease in MMP were detected. RESULTS After being treated with oxymatrine， the apoptotic rate， the protein expressions of Bax， PINK1， Parkin， and LC3-Ⅱ， the level of mitophagy as well as the proportion of decrease in MMP were significantly increased （P＜0.05）， while the protein expression of Bcl-2 was significantly decreased （P＜0.05）. Compared with the oxymatrine group， the protein expressions of PINK1， Parkin， and LC3-Ⅱ， apoptotic rate and the proportion of decrease in MMP were significantly decreased in PINK1 siRNA+oxymatrine group （P＜0.05）. Compared with the oxymatrine group， the protein expression of COX-2 in the COX-2+oxymatrine group was increased significantly （P＜0.05）， while the protein expressions of PINK1 and Parkin as well as the proportion of 526087266@qq.com decrease in MMP were decreased significantly （P＜0.05）. CONCLUSIONS Oxymatrine can mediate the overactivity of mitophagy based on the PINK1/Parkin signaling pathway by inhibiting COX-2 expression， thus promoting the apoptosis of the MG63 osteosarcoma cell line.
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Background: Epilepsy is an abnormal excessive electric neuronal activity and always represents by recurrent seizures. There is positive feedback cycle between epileptogenesis and brain inflammation. It has been proved that an inflammatory enzyme, cyclooxygenase (COX) (especially isoform-2, a constitutive enzyme), expressed in some important parts of the central nervous system and is responsible to induced inflammation locally and having seizurogenic property. Aim and Objective: The goal of this study was to see if celecoxib (a selective COX-2 inhibitor) could reduce the maximal electroshock seizure (MES)-induced seizures in mice. Materials and Methods: Celecoxib injected intraperitoneally in two different doses 5 mg/kgb/w and 10 mg/kg b/w, in albino Swiss mice and in two different phases. MES was elicited and length of different phases was noted. Length of tonic hindlimb extension was considered as indicator of anti-epileptic activity. Results: Celecoxib, when given intraperitoneally, exert significant reduction in the duration of THLE. This action of celecoxib strongly suggests the involvement of inflammation in the pathophysiology of epilepsy. Conclusion: The findings are suggestive of the therapeutic significance of celecoxib, as a future antiepileptic agent for seizure management.
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Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD) which is increasing worldover due to modern life style. Patients with UC are prone to develop colorectal cancer. While the disease severity decides the treatment option, researchers look towards herbal medicines with anti-inflammatory properties for minimal or nil side effects. Artemisia dracunculus L., commonly called Tarragon, is a medicinal herb used in traditional Asian medicine mainly in Iran, India, Pakistan and Azerbaijan due to its special compounds. In this study, we tried to elucidate the effects of aqueous extract of tarragon on acetic acid induced ulcerative colitis (UC) in rats. Male Wistar rats were grouped into four groups of eight each viz., control; experimental control (UC was induced via luminal instillation of 4% acetic acid); and UC induced + aqueous tarragon extract (100 mg/kg) or prednisolone (2 mg/kg) orally for ten consecutive days. Tissue specimens were collected after the experimental period for evaluation of caspase-3 and cyclooxygenase-2 (COX-2) expression by immunohistochemistry. Real-time PCR was used to monitor the levels of IL-1, IL-6 and TNF-? in colonic homogenates. Moreover, the levels of myeloperoxidase, nitric oxide and total antioxidant capacity were measured in colonic homogenates. The results showed that both treatment regimens could similarly reduce the severity of disease symptoms. Treatment with aqueous extract of tarragon caused a better improvement (P <0.05) in the levels of myeloperoxidase enzyme, and total antioxidant capacity of colonic homogenates compared to prednisolone. Nevertheless, the levels of the expression of caspase-3, and COX-2 and TNF-? were reduced in UC rats received prednisolone more than UC rats received aqueous extract of tarragon. The was no statistical difference in the levels of nitric oxide, IL-1 and IL-6 between UC rats received tarragon extract or prednisolone. Overall, these findings suggest that the aqueous extract of tarragon is a promising strategy to control ulcerative colitis. Aqueous extract can also be used as an anti-inflammatory and immune system stimulant in conditions where the immune system is damaged.
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Abstract Objective To explore the potential for development of Thai propolis extract as a pulp capping agent to suppress pulpal inflammation from dental pulp infections. This study aimed to examine the anti-inflammatory effect of the propolis extract on the arachidonic acid pathway, activated by interleukin (IL)-1β, in cultured human dental pulp cells. Methodology Dental pulp cells, isolated from three freshly extracted third molars, were first characterized for their mesenchymal origin and treated with 10 ng/ml of IL-1β in the presence or absence of non-toxic concentrations of the extract from 0.08 to 1.25 mg/ml, as determined by the PrestoBlue cytotoxic assay. Total RNA was harvested and analyzed for mRNA expressions of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2). Western blot hybridization was performed to investigate COX-2 protein expression. Culture supernatants were assayed for released prostaglandin E2 levels. Immunofluorescence was conducted to determine involvement of nuclear factor-kappaB (NF-kB) in the inhibitory effect of the extract. Results Stimulation of the pulp cells with IL-1β resulted in the activation of arachidonic acid metabolism via COX-2, but not 5-LOX. Incubation with various non-toxic concentrations of the propolis extract significantly inhibited upregulated COX-2 mRNA and protein expressions upon treatment with IL-1β (p<0.05), resulting in a significant decrease in elevated PGE2 levels (p<0.05). Nuclear translocation of the p50 and the p65 subunits of NF-kB upon treatment with IL-1β was also blocked by incubation with the extract. Conclusions Upregulated COX-2 expression and enhanced PGE2 synthesis upon treatment with IL-1β in human dental pulp cells were suppressed by incubation with non-toxic doses of Thai propolis extract via involvement of the NF-kB activation. This extract could be therapeutically used as a pulp capping material due to its anti-inflammatory properties.
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ABSTRACT Objective: To investigate the association between single nucleotide polymorphisms in the COX2 gene (rs689466 and rs5275) and local and systemic signs and symptoms of teething. Material and Methods: Forty-four pairs of mothers-babies/toddlers were included. Erupted primary teeth were evaluated during clinical examination. Local and systemic signs and symptoms of teething were obtained from mothers' reporting via anamnesis. Samples of buccal cells were retrieved for DNA genotyping using real-time PCR. The T-test, Chi-square test, logistic regression, and haplotype analyses were applied. Results: Almost all mothers (95.5%) reported at least one local or systemic sign and symptom of teething. The most common was increased salivation (79.5%), diarrhea (72.3 %), and fever (70.5 %). The mean number of signs and symptoms per child was higher in boys than girls (mean = 5.1; SD= 1.5; p=0.008). Sleep disturbance (p=0.03) and loss of appetite (p=0.05) were more reported in boys. The rs689466 and rs5275 were not associated with signs and symptoms of teething (p>0.05). Conclusion: The single nucleotide polymorphisms in the COX2 gene (rs689466 and rs5275) were not associated with local and systemic signs and symptoms of teething.
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Humans , Male , Female , Infant , Child, Preschool , Sleep Wake Disorders , Tooth, Deciduous/anatomy & histology , Tooth Eruption , Polymorphism, Single Nucleotide , Chi-Square Distribution , Cross-Sectional Studies/methods , MothersABSTRACT
ObjectiveTo observe the glucose-lowering， insulin resistance-improving， and anti-inflammatory effects of flavonoids from mulberry leaves （FML） and explore their underlying mechanism. MethodMale db/db mice aged 6-7 weeks were randomly divided into a model group， a high-dose FML group （1.00 g·kg·d-1）， and a low-dose FML group （0.50 g·kg-1·d-1）. C57BL mice of the same age were assigned to the normal group. After six weeks of intervention， fasting blood glucose （FBG）， serum fasting insulin levels （Fins）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， free fatty acid （FFA）， blood creatinine （SCr）， blood urea nitrogen （BUN）， and aspartate aminotransferase （AST） levels were measured， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and catalase activities in the liver were measured. Morphological changes in the liver were assessed by hematoxylin-eosin （HE） staining. The protein expression of cyclooxygenase-2 （COX-2）， inducible nitric oxide synthase （iNOS）， and nuclear factor-κB （NF-κB） in the liver was detected by Western blot. ResultCompared with the model group， the high-dose and low-dose FML groups showed significant reductions in FBG， Fins， HOMA-IR， IL-6， TNF-α， and FFA levels （P<0.05， P<0.01）， and increased levels of SOD， GSH-Px， and catalase in the liver （P<0.05， P<0.01）. HE staining of the liver in the FML groups showed improved arrangement of hepatocytes， reduced inflammatory cell infiltration， and alleviated cellular steatosis compared with the model group. The protein expression of COX-2， iNOS， and NF-κB in the liver significantly decreased in the FML groups as compared with that in the model group （P<0.05， P<0.01）. ConclusionFML have glucose-lowering and insulin resistance-improving effect， which may be attributed to their regulation of the NF-κB pathway in the liver of diabetic mice， leading to the suppression of the release of COX-2， iNOS， and inflammatory cytokines， thereby improving the inflammatory state.
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ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets （TWPT） in the prevention and treatment of kidney injury in diabetic nephropathy （DN） through the nuclear factor of activated T-cells 2（NFAT2）/cyclooxygenase-2（COX-2） pathway. MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group （n=8） and an experimental group （n=34） after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin （STZ） following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated， the remaining 24 model rats were randomly divided into model group， valsartan （8.33 mg·kg-1·d-1） group， and TWPT （5 mg·kg-1·d-1） group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks， body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta， and then the rats were sacrificed for sampling. Biochemical indicators， such as serum blood urea nitrogen （BUN）， serum creatinine （SCr）， alanine aminotransferase （ALT）， blood lipid， blood glucose， and 24-hour urine total protein （24 h UTP）， were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay （ELISA） was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were adopted to detect NFAT2， COX-2 protein and mRNA expression in kidney tissues， respectively. ResultCompared with the normal group， the model group showed elevated 24 h UTP， BUN， SCr， CHO， TG， and FBG， increased serum NFAT2 and COX-2 production and expression （P<0.01）， and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）. In addition， the pathology of the kidney showed enlarged glomeruli， mild proliferation of mesangial cells， and widened mesangial stroma. Compared with the model group， the TWPT group showed decreased 24 h UTP， BUN， SCr， CHO， TG， and FBG （P<0.05，P<0.01）， basically normal glomerular morphology， decreased expression of serum NFAT2 and COX-2 （P<0.01）， and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）. ConclusionTWPT can alleviate 24 h UTP in DN model rats， protect renal function， and improve renal pathology， and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.
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OBJECTIVE@#To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of β-endorphin (β-EP), substance P (SP) and expression of interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine.@*METHODS@#Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of β-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1β in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem.@*RESULTS@#Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of β-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of β-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of β-EP was increased and COX-2 protein expression was decreased (P<0.05).@*CONCLUSION@#Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1β and COX-2 protein expression in brainstem, and increase the serum level of β-EP, and the optimal effect is observed in the PT group.
Subject(s)
Rats , Male , Animals , Moxibustion , Rats, Sprague-Dawley , Cyclooxygenase 2 , beta-Endorphin , Substance P , Interleukin-1beta , Migraine Disorders , Brain StemABSTRACT
Abstract Background In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. Objective To evaluate the correlation of COX-2 with the prognosis in glioma patients. Methods Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. Results In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79-2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57-2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69-3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. Conclusion The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice.
Resumo Introdução Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. Objetivo Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. Métodos Estudos elegíveis sobre este assunto foram incluídos e foram estimadosodds ratios (ORs) ehazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. Resultados No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57-2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69-3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. Conclusão O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica.
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Background: Oral lichen planus (OLP) is a chronic inflammatory disease for which the pathogenesis is complex and not fully understood; autoimmunity has been suggested as a causative factor. World health organization (WHO) has classified OLP as a potentially malignant lesion. Cyclooxygenase-2 (COX-2) is an inducible key enzyme that generates prostanoids which play a critical role in inflammation, immunopathology; also considered as a malignant potential marker. Aims: The present study was conducted to analyze and compare epithelial COX-2 expression in OLP clinical subtypes and normal oral mucosa to evaluate its role in the pathophysiology of the disease process. Methods: This retrospective immunohistochemistry (IHC) study was performed on tissue sections of 30 OLP and 10 normal oral mucosae for COX-2 expression. Statistical Analysis Used: Descriptive and comparative statistical methods were done using 'one-way Analysis of Variance (ANOVA), 't' and Chi-square tests. Results: All the OLP showed epithelial COX-2 expression; strong expression was noted in 80% of the OLP while normal oral mucosa sections showed no expression. Cox-2 expression was significantly higher in erosive lichen planus compared to reticular lichen planus. Conclusions: Strong expression of COX-2 in OLP suggested its important role in pathogenesis. Although COX-2 has been connected to malignant development and autoimmunity, as the malignant development in OLP is quite rare, this study suggests that increased levels of COX-2 seen here may support an autoimmune cause of the disease process.
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Objective:To investigate the expression of miR-211-5p in peripheral blood of patients with myelosuppression after neoadjuvant chemotherapy for breast cancer and its effect on Notch signaling pathway by targeting cyclooxygenase 2 (COX2) gene Regulation mechanism.Methods:From Jan. 2018 to Jan. 2021, 185 breast cancer patients who received neoadjuvant chemotherapy in Linyi People’s Hospital for the first time were included as the research objects. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the mRNA expression levels of miR-211-5p, COX2 gene and Notch signaling pathway related genes (Notch1, Jagged1 and Hes1) . The miR-211-5p mimic, inhibitor, mimic NC, and inhibitor NC were transfected into SD rat bone marrow mesenchymal stem cells, and the mRNA expression of miR-10a-3p and COX2 genes was detected by qRT-PCR for 48 hours. Western blot method was used to detect the protein expression levels of Notch signaling pathway related genes.Results:The relative expression of miR-211-5p in patients with severe myelosuppression was 2.41±0.32, which was significantly higher than that in patients with mild myelosuppression (1.53±0.18) ( t=6.385, P<0.001) ; The relative expression of COX2 gene mRNA in patients with severe myelosuppression was 3.64±0.74, which was significantly lower than that in patients with mild myelosuppression (5.37±1.02) ( t=7.469, P<0.001) . In patients with severe myelosuppression, there was a significant negative correlation between miR-211-5p and COX2 gene mRNA levels ( r=-0.694, P=0.006) . The results of the dual luciferase report experiment confirmed that COX2 was the target gene of miR-211-5p. The relative expression of Notch1, Jagged1, and Hes1 mRNA in peripheral blood of patients with severe myelosuppression were 2.35±0.41, 2.76±0.46 and 3.04±0.52, respectively, which were significantly lower than those in patients with mild myelosuppression (4.12±0.63, 4.53±0.58 and 5.12±0.67) ( t=5.367, 6.114 and 6.135, respectively, P<0.001) . After transfecting SD rat bone marrow mesenchymal stem cells with miR-211-5p mimics and inhibitors, the relative expression of miR-211-5p in the mimic group was 3.46±0.49, significantly higher than that in the mimic NC group (2.24±0.32) The relative expression of miR-211-5p in the inhibitor group was (1.28±0.19) and (2.33±0.37) inhibitor NC group ( P<0.001) , while the relative expression of miR-211-5p in the inhibitor group was significantly lower than that in the other three groups ( P<0.001) . The mRNA expression of COX2 gene in mimic group was 2.73±0.36, which was significantly lower than that in mimic NC group (4.05±0.59) , inhibitor group (6.15±0.86) and inhibitor NC group (4.18±0.65) ( P<0.001) , while mRNA expression of COX2 gene in the inhibitor group was significantly higher than that in the other three groups ( P<0.001) . The expression of Notch1, Jagged1, and Hes1 in the inhibitor group was significantly increased, while the expression of Notch1, Jagged1, and Hes1 in the mimic group was significantly decreased. Conclusion:The expression level of miR-211-5p in peripheral blood of severe myelosuppressed patients with breast cancer after neoadjuvant chemotherapy is significantly increased, and the Notch signaling pathway can be inhibited by targeted down-regulation of COX2 gene expression.
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Objective:To investigate the effects of preoperative administration of parecoxib sodium on stress reaction and postoperative nausea and vomiting score in patients undergoing laparoscopic cholecystectomy.Methods:A total of 112 patients undergoing laparoscopic cholecystectomy in Lishui City People's Hospital from January 2020 to January 2021 were included in this study. They were randomly divided into observation group and control group, with 56 patients per group. The observation group was intravenously administered 40 mg parecoxib sodium 30 minutes before surgery, and the control group was identically administered equal amount of 0.9% sodium chloride injection. At 1, 6, 12 and 24 hours after surgery, Visual Analogue Scale (VAS) score, cortisol and adrenocorticotropic hormone levels and postoperative nausea and vomiting score were compared between the two groups.Results:At 1, 6 and 12 hours after surgery, VAS score in the observation group was (3.23 ± 0.85) points, (2.44 ± 0.76) points, (2.37 ± 0.69) points, respectively, which were significantly lower than (4.06 ± 1.12) points, (3.24 ± 0.95) points, (3.10 ± 1.07) points in the control group ( t = 4.41, 4.92, 4.29, all P < 0.001). At 1, 6, 12 and 24 hours after surgery, cortisol level in the observation group was (287.79 ± 35.46) ng/L, (303.55 ± 34.77) ng/L, (368.58 ± 31.22) ng/L, (397.16 ± 32.60) ng/L, respectively, which were significantly lower than (337.64 ± 39.52) ng/L, (364.18 ± 36.90) ng/L, (405.56 ± 37.29) ng/L, (455.51 ± 37.81) ng/L in the control group ( t = 7.02, 8.94, 5.69, 8.74, all P < 0.05). At 1, 6, 12 and 24 hours after surgery, adrenocorticotropic hormone level in the observation group was (59.25 ± 7.63) ng/L, (65.27 ± 8.23) ng/L, (72.29 ± 7.49) ng/L, (83.63 ± 8.57) ng/L, which were significantly lower than (64.48 ± 8.06) ng/L, (71.44 ± 8.59) ng/L, (79.79 ± 8.15) ng/L, (90.08 ± 8.26) ng/L in the control group ( t = 3.52, 3.88, 5.07, 4.05, all P < 0.05). Within 24 hours after surgery, the incidence of postoperative nausea and vomiting in the observation group was significantly lower than that in the control group [12.50% (7/56) vs. 28.57% (16/56), χ2 = 4.43, P < 0.05). Within 2 hours, 2-6 hours, and > 6-24 hours, postoperative nausea and vomiting score in the observation group was (1.31 ± 0.26) points, (1.43 ± 0.32) points, and (1.46 ± 0.41) points, respectively, which was significantly lower than (1.67 ± 0.41) points, (1.83 ± 0.39) points, (1.88 ± 0.44) points in the control group ( t = 2.12, 2.37, 2.14, all P < 0.05). Conclusion:Preoperative administration of parecoxib sodium exhibits a good postoperative analgesic effect in patients undergoing laparoscopic cholecystectomy. It can effectively reduce postoperative stress reactions, decrease the incidence of postoperative nausea and vomiting, and lower the severity of postoperative nausea and vomiting, and thereby can be widely used in clinical practice.
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OBJECTIVES@#Percutaneous coronary intervention (PCI) is one of the important methods for the treatment of coronary artery disease (CAD). In-sent restenosis (ISR) after PCI for patients suffered from CAD is considered to be an essential factor affecting long-term outcomes and prognosis of this disease. This study aims to investigate the correlation between plasma Quaking (QKI) and cyclooxygenase-2 (COX-2) levels and ISR in patients with CAD.@*METHODS@#A total of 218 consecutive CAD patients who underwent coronary angiography and coronary arterial stenting from September 2019 to September 2020 in the Department of Cardiology of Xiangya Hospital of Central South University were enrolled in this study, and 35 matched individuals from the physical examination center were served as a control group. After admission, clinical data of these 2 groups were collected. Plasma QKI and COX-2 levels were measured by enzyme linked immunosorbent assay (ELISA). Follow-up angiography was performed 12 months after PCI. CAD patients were divided into a NISR group (n=160) and an ISR group (n=58) according to the occurrence of ISR based on the coronary angiography. The clinical data, coronary angiography, and stent features between the NISR group and the ISR group were compared, and multivariate logistic regression was used to explore the factors influencing ISR. The occurrence of major adverse cardiovascular events (MACE) 1 year after operation was recorded. Fifty-eight patients with ISR were divided into an MACE group (n=24) and a non-MACE group (n=34), classified according to the occurrence of MACE, and the plasma levels of QKI and COX-2 were compared between the 2 groups. Receiver operating characteristic (ROC) curves were utilized to analyze the diagnostic value of plamsa levels of QKI and COX-2 for ISR and MACE occurrences in patients after PCI.@*RESULTS@#Compared with control group, plasma levels of QKI and COX-2 in the CAD group decreased significantly (all P<0.001). Compared with the NISR group, the plasma levels of QKI and COX-2 also decreased obviously in the ISR group (all P<0.001), while the levels of high sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin (HbAlc) significantly increased (all P<0.001). The level of COX-2 was negatively correlated with hs-CRP (r=-0.385, P=0.003). Multivariate logistic regression analysis showed that high level of plasma QKI and COX-2 were protective factors for in-stent restenosis after PCI, while hs-CRP was a risk factor. ROC curve analysis showed that the sensitivity and specificity of plasma QKI for evaluating the predictive value of ISR were 77.5% and 66.5%, respectively, and the sensitivity and specificity of plasma COX-2 for evaluating the predictive value of ISR were 80.0% and 70.7%, respectively. The sensitivity and specificity of plasma QKI combined with COX-2 for evaluating the predictive value of ISR were 81.3% and 74.1%, respectively. The sensitivity and specificity of plasma QKI for evaluating the prognosis of ISR were 75.0% and 64.7%, respectively. The sensitivity and specificity of plasma COX-2 for evaluating the prognosis of ISR were 75.0% and 70.6%, respectively. The sensitivity and specificity of plasma QKI combined with COX-2 for prognostic evaluation of ISR were 81.7% and 79.4%, respectively. The sensitivity and specificity of plasma COX-2 combined with QKI for evaluating ISR and MACE occurrences in patients after PCI were better than those of COX-2 or QKI alone (P<0.001).@*CONCLUSIONS@#High level of plasma QKI and COX-2 might be a protective factor for ISR, which can also predict ISR patient's prognosis.
Subject(s)
Humans , C-Reactive Protein/analysis , Constriction, Pathologic/etiology , Coronary Angiography/adverse effects , Coronary Artery Disease , Coronary Restenosis/therapy , Cyclooxygenase 2 , Percutaneous Coronary Intervention/adverse effects , Risk Factors , Stents/adverse effectsABSTRACT
Objective:To evaluate the effect of propofol on proliferation, invasion and migration of human melanoma cells and role of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/matrix metalloproteinase (MMP) signaling pathway.Methods:SKMEL-5 cells were cultured in vitro and divided into 4 groups ( n=36 each) using the random number table method: control group (group C), propofol group (group P), COX-2 overexpression group (group COX-2), and COX-2 overexpression plus propofol group (group COX-2+ P). Propofol at the final concentration of 60 μmol/L was added in group P. The COX-2 overexpression plasmid pcDNA3.1-COX-2 was transfected into SKMEL-5 cells in group COX-2 and group COX-2+ P, and propofol at the final concentration of 60 μmol/L was added in group COX-2+ P.After incubation for 48 h, the cell proliferation rate was determined by CCK-8 method, the cell invasion and migration ability was determined by Transwell assay, the expression of COX-2 in cells was detected by Western blot, the expression of COX-2 mRNA in cells was detected by quantitative real-time polymerase chain reaction, and the concentrations of serum PGE2, MMP-2 and MMP-9 were determined by enzyme-linked immunosorbent assay. Results:Compared with group C, the cell proliferation rate was significantly decreased, the number of cell invasion and migration was decreased, the expression of COX-2 protein and mRNA was down-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were decreased in group P, and the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2 ( P<0.05). Compared with group P, the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2+ P ( P<0.05). Conclusions:Propofol can inhibit the proliferation, invasion and migration of human melanoma cells, and the mechanism may be related to inhibition of the COX-2/PGE2/MMP signaling pathway.
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Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.
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RESUMEN Introducción: El uso de TNFi es cada vez más frecuente en los pacientes con espondiloartritis. Identificar tempranamente aquellos que los requerirán o poder predecir su uso puede ayudar a hacer un tratamiento más efectivo y oportuno racionalizando su uso. Objetivo: Determinar los factores qué mejor explican la indicación de TNFi en la población en estudio. Material y métodos: La asociación entre el uso de medicamentos anti-TNFα y las variables categóricas demográficas, clínicas, de laboratorio, radiológicas y de tratamiento se exploró por prueba exacta de Fisher. La asociación con las variables cuantitativas fue evaluada con t de Student o U de Mann Withney, de acuerdo con su distribución. Aquellas variables con p < 0,25 fueron ingresadas a modelos univariante de regresión logística explicativa para construir los OR crudos; aquellas con p < 0,25 se incluyeron en el modelo multivariante para construir OR ajustados. Resultados y discusión: La población está constituida por 181 pacientes. Modelo univariante: la artritis reactiva, uretritis y compromiso periférico fueron factores protectores para el uso de TNFi. Espondiloartritis axial, lumbalgia inflamatoria, dolor glúteo alternante, rigidez matinal sacroilitis demostrada por cualquier método, tratamiento con inhibidores COX-2, tiempo de evolución de tres arios o más y los puntajes de BASDAI y BASFI se asociaron con el uso de TNFi. Modelo multivariante: artritis reactiva (OR 0,1, IC 95% 0,012-0,86, p = 0,036), lumbalgia inflamatoria (OR 13,63, IC 95% 1,36-136, p = 0,026), sacroilitis (OR 7,71, IC 95% 1,04-57, p = 0,045, uso de coxib (OR 10,1, IC 95% 2,71-37,62, p = 0,001) y el puntaje máximo de BASDAI (4-6: OR 6,1, IC 95% 1,3-28,7, p = 0,022, mayor de 6: OR 15,8, IC 95% 2,2-113, p = 0,006) se asociaron independientemente con el uso de TNFi. El uso de coxib se asoció con la indicación de usar TNFi tanto en los pacientes con espondiloartritis axial (OR 4,2, IC 95% 1,74-10,11, p = 0,001) como periférica (OR 4, IC 95% 1,85-8,62, p < 0,001). Conclusiones: El inicio de la enfermedad en la forma de artritis reactiva se comportó como un factor protector para la necesidad posterior de usar TNFi, mientras que presentar lumbalgia inflamatoria, sacroilitis demostrada por cualquier método, el tratamiento con coxib y el puntaje máximo de BASDAI mayor de 4 se asociaron con el uso de estos medicamentos.
ABSTRACT Introduction: The use of tumor necrosis factor (TNF) alpha inhibitors is increasing in patients with spondyloarthritis. Early identification of those that would require them, or the ability to predict their use, could lead to a more effective and timely treatment by rationalizing their use. Objective: To determine factors that better explain the indication of TNFi in the study population. Material and methods: The association between anti-TNFα use and categorical demographic, clinical, laboratory, radiological and treatment variables was explored using Pearson's Chi2 or Fisher's exact test. The association with the quantitative variables was evaluated using Student's t test or Mann Whitney U test, depending on their distribution. Those variables with P < 0.25 were entered into univariate models of explanatory logistic regression to cons truct crude ORs, and those with P < 0.25 were included in the multivariate model to construct adjusted ORs. Results and discussion: The study population includes 181 patients. In the univariate model: reactive arthritis, urethritis, and peripheral involvement were protective factors for the use of TNFi. Axial spondyloarthritis, inflammatory lumbalgia, alternating gluteal pain, morning stiffness, sacroiliitis demonstrated by any method, treatment with COX-2 inhibitors, evolu tion time of three years or more, and BASDAI and BASFI scores were associated with the use of TNFi. Multivariate model: reactive arthritis (P = 0.036), inflammatory back pain (P = 0.026), sacroiliitis (P = 0.045), use of coxibs (P = 0.001) and the maximum score of BASDAI (P = 0.022, P = 0.006) were independently associated with the use of TNFi. The use of coxibs was associa ted with the indication of using TNFi in both patients with axial spondyloarthritis (P = 0.001) and peripheral (P < 0.001). Conclusions: The onset of the disease in the form of reactive arthritis behaved as a protective factor for the subsequent need to use TNFi, while presenting with inflammatory back pain, sacroiliitis, demonstrated by any method, treatment with coxibs, and the maximum score of BASDAI greater than 4 associated with the use of these medications.
Subject(s)
Humans , Adult , Bone Diseases , Musculoskeletal Diseases , SpondylarthritisABSTRACT
Based on the heat-clearing and detoxifying effects of Gentianae Radix et Rhizoma, the network pharmacology is mainly used to predict the potential targets of Gentianae Radix et Rhizoma for anti-inflammatory activity and to perform the experimental verification. A method for detecting the biological potency of Gentianae Radix et Rhizoma based on verifiable targets has been established to provide a reference for improving the quality evaluation and control standards of Gentianae Radix et Rhizoma. High performance liquid chromatography can be used to construct chemical fingerprints of different batches of Gentianae Radix et Rhizoma. Constructing a component-target-disease network of Gentianae Radix et Rhizoma for its anti-inflammatory activity was applied to screen potential anti-inflammatory components and related targets of Gentianae Radix et Rhizoma, and to verify the target of Gentianae Radix et Rhizoma by using biological evaluation methods. Detecting the biological potency of different batches of Gentianae Radix et Rhizoma extracts was used to inhibit COX-2 enzyme activity based the verifiable target cyclooxygenase-2(COX-2). The results showed that different batches of Gentianae Radix et Rhizoma accorded with the pharmacopoeia testing regulations, and the chemical fingerprints have a high similarity(similarity>0.93), suggesting that there is no significant difference in the characteristics of the chemical components. Based on network pharmacology predictions, 18 candidate targets were found to have potential direct interactions with the ingredients in Gentianae Radix et Rhizoma. Among them, the most important target is COX-2. Based on the experimental verification of recombinant human COX-2 protease activity inhibition, Gentianae Radix et Rhizoma can inhibit the COX-2 enzyme activity in a dose-dependent manner. It can function with a low concentration(0.75 mg·mL~(-1)), which preliminarily confirmed the accuracy of network pharmacology prediction. The biological potency detection method of Gentianae Radix et Rhizoma based on COX-2 inhibitory activity was optimized and established. The qualitative response parallel line method was used to calculate the biological potency of anti-inflammatory activity, which ranged from 23.04 to 46.60 U·mg~(-1). For network pharmacology prediction, it can screen and clarify the possible targets of traditional Chinese medicine rapidly, which can guide the establishment of a biological evaluation method for the quality of medicinal materials with related activities. Compared with chemical fingerprints, the biological potency testing can better detect quality fluctuations of traditional Chinese medicine.
Subject(s)
Humans , Anti-Inflammatory Agents/pharmacology , Biological Assay , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Quality Control , RhizomeABSTRACT
Objective:To explore the effects of Ophiopogon D combined with cyclooxygenase-2 (COX-2) gene silencing on the proliferation, migration and invasion of human pancreatic cancer BxPC-3 cells.Methods:BxPC-3 cells were divided into blank control group, Ophiopogonin D high-dose group (40 μmol/L), medium-dose group (20 μmol/L) and low-dose group (10 μmol/L). The COX-2-slienced cells were divided into control group, COX-2 inhibited group (50 pmol/ml siRNA-COX-2), Ophiopogonin D group (20 μmol/L) and combination treatment group (Ophiopogonin D 20 μmol/L+ 50 pmol/ml siRNA-COX-2). The proliferation activity of BxPC-3 cells was detected by CCK-8, and the migration distance of BxPC-3 cells was detected by scratched assay. The invasion degree of BxPC-3 cells was detected by Transwell, the relative expression level of COX-2 gene in BxPC-3 cells was detected by real-time quantitative PCR (RT-qPCR), and the relative expressions of COX-2, hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins in BxPC-3 cells were detected by Western blotting.Results:The cell proliferation rates of blank control group, Ophiopogonin D high-dose, medium-dose and low-dose groups were (100.0±4.9)%, (71.8±5.4)%, (80.5±5.8)% and (89.7±5.7)%, respectively. The migration distances were (279.8±24.0) μm, (141.9±21.2) μm, (168.8±37.1) μm and (224.6±19.9) μm, respectively. The absorbance ( A) values of invasion number were 1.107±0.095, 0.390±0.030, 0.596±0.017 and 0.826±0.034, respectively.There were statistically significant differences ( F=19.770, P<0.001; F=48.270, P<0.001; F=198.400, P<0.001). The above indexes of the Ophiopogonin D high-, medium- and low-dose groups were significantly lower than those in the blank control group (all P<0.05). The relative expression levels of COX-2 gene were 1.007±0.178, 0.387±0.169, 0.567±0.142 and 0.740±0.030, respectively, and the relative protein expression levels were 1.000±0.033, 0.654±0.085, 0.762±0.110 and 0.881±0.049, respectively, with statistically significant differences ( F=10.280, P=0.004; F=11.780, P=0.003). The above indexes of the Ophiopogonin D high- and medium-dose groups were significantly lower than those in the blank control group (all P<0.05), and there was no statistically significant difference between the Ophiopogonin D low-dose group and blank control group (both P>0.05). The medium-dose of Ophiopogonin D (20 μmol/L) was selected as the subsequent concentration.After COX-2 silencing, the proliferation rates of the control group, COX-2 inhibited group, Ophiopogonin D group and combination treatment group were (100.0±2.8)%, (68.4±6.7)%, (67.7±5.9)% and (57.0±8.5)%, respectively, the migration distances were (274.4±23.8) μm, (217.0±18.8) μm, (186.2±18.6) μm and (115.7±15.8) μm, respectively, and the A values of invasion number were 1.143±0.092, 0.791±0.058, 0.715±0.026 and 0.424±0.058, respectively, with statistically significant differences ( F=34.430, P<0.001; F=103.400, P<0.001; F=131.100, P<0.001). The proliferation rates, migration distances and invasion numbers in each treatment group were significantly lower than those in the control group (all P<0.001). Compared with the COX-2 inhibited group and Ophiopogonin D group, the cell proliferation, migration and invasion were significantly inhibited in the combination treatment group (all P<0.05). Compared with the Ophiopogonin D group, only the migration distance of the COX-2 inhibited group was significantly different ( P<0.05). The relative expression levels of COX-2 protein in the above groups were 0.995±0.037, 0.779±0.060, 0.806±0.076 and 0.645±0.079, respectively, the relative expression levels of HIF-1α were 1.083±0.104, 0.749±0.070, 0.736±0.070 and 0.394±0.016, respectively, and the relative expression levels of VEGF protein were 1.016±0.103, 0.757±0.090, 0.745±0.021 and 0.603±0.023, respectively, with statistically significant differences ( F=14.650, P=0.001; F=45.220, P<0.001; F=18.180, P<0.001). The expression levels of the three proteins in each treatment group were significantly lower than those in the control group (all P<0.05). Compared with the COX-2 inhibited group and Ophiopogonin D group, the relative protein expression levels of COX-2, HIF-1α and VEGF in the combination treatment group were significantly decreased (all P<0.05). Compared with the Ophiopogonin D group, there were no significant differences in the expression of the three proteins in the COX-2 inhibited group (all P>0.05). Conclusion:Ophiopogon D combined with COX-2 gene silencing can inhibit the proliferation, migration and invasion of pancreatic cancer cells, and the mechanism may be related to the inhibition of COX-2 pathway and the decrease of HIF-1α and VEGF protein expression levels.
ABSTRACT
Xiaoer-Feire-Kechuan (XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the anti-inflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were estab-lished and validated to quantify 35 analytes (covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A (8-10),and baicalin (15) (total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities (inhibitory rate ≥ 80％) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.
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Context: Osteosarcoma (OS) is a progressive primary bone tumor that originates from immature stromal spindle cells. After chemotherapy, the serum-related indexes which are related to the prognosis. Aims: The aim of this study is to investigate the correlation between changes in serum cyclooxygenase-2 (COX-2), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and tumor-specific growth factor (TSGF) levels and prognosis of patients with osteosarcoma (OS) before and after treatment. Settings and Design: Data of 75 patients with OS (observation group) and 55 healthy controls (control group) were retrospectively analyzed. Materials and Methods: Chemotherapy was administered to the observation group. Serum lactate dehydrogenase, alkaline phosphatase, and TSGF levels were measured before and after treatment. The observation group patients were classified as normal or abnormal according to the changes in serum COX-2, bFGF, VEGF, TGF-β, and TSGF levels after chemotherapy. Patients were followed up for 7.5 years, and the survival rate was determined. Statistical Analysis Used: Single-factor influencing prognosis was included in the Cox model, and independent factors influencing prognosis were analyzed. Results: After chemotherapy, the mean serum COX-2, bFGF, VEGF, and TSGF levels decreased significantly in the observation group but were still higher than those in the control group. Furthermore, serum TGF-β levels increased in the observation group but were still lower than those in the control group. The 5-year survival rate of patients with normal serum COX-2, bFGF, VEGF, and TSGF levels was significantly higher in the normal subgroup than in the abnormal subgroup. Cox analysis showed that the Enneking stage and COX-2 level after chemotherapy were independent prognostic factors. Conclusions: The serum COX-2, bFGF, VEGF, and TSGF levels of patients with OS significantly changed after chemotherapy, and the short-term survival rate of patients with normal levels of these biomarkers after chemotherapy was high