Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Sequence analysis of Paragonimus internal transcribed spacer 2 and cyclooxygenase 1 genes in freshwater crabs in Henan Province / 中国血吸虫病防治杂志

Objective To investigate the sequences of internal transcribed spacer 2 (ITS2) and cyclooxygenase 1 (COX1) genes of Paragonimus metacercariae in freshwater crabs in Henan Province, identify the species of Paragonimus and evaluate its genetic relationships with Paragonimus isolates from other provinces in China. Methods Freshwater crabs were collected from 8 survey sites in Zhengzhou, Luoyang, Pingdingshan, Nanyang and Jiyuan cities of Henan Province from 2016 to 2021, and Paragonimus metacercariae were detected in freshwater crabs. Genomic DNA was extracted from Paragonimus metacercariae, and the ITS2 and COX1 genes were amplified using PCR assay, followed by sequencing of PCR amplification products. The gene sequences were spliced and aligned using the software DNASTAR, and aligned with the sequences of Paragonimus genes in the GenBank. Phylogenetic trees were created using the MEGA6 software with the Neighbor-Joining method based on ITS2 and COX1 gene sequences, with Fasciola hepatica as the outgroup. Results The detection rates of Paragonimus metacercariae were 6.83% (11/161), 50.82% (31/61), 18.52% (5/26), 8.76% (12/137), 14.29% (9/63), 17.76% (19/105), 18.50% (32/173) and 42.71% (41/96) in freshwater crabs from 8 survey sites in Zhengzhou, Luoyang, Pingdingshan, Nanyang and Jiyuan cities of Henan Province, with a mean detection rate of 19.46% (160/822), and a mean infection intensity of 0.57 metacercariae/g. The amplified ITS2 and COX1 gene fragments of Paragonimus were approximately 500 bp and 450 bp in lengths, respectively. The ITS2 gene sequences of Paragonimus metacercariae from 8 survey sites of Henan Province showed the highest homology (99.8% to 100.0%) with the gene sequence of P. skrjabini (GenBank accession number: MW960209.1), and phylogenetic analysis showed that the Paragonimus in this study was clustered into the same clade with P. skrjabini from Sichuan Province (GenBank accession number: AY618747.1), Guangxi Zhuang Autonomous Region (GenBank accession number: AY618729.1) and Hubei Province (GenBank accession number: AY618751.1), and P. miyazaki from Fujian Province (GenBank accession number: AY618741.1) and Japan (GenBank accession number: AB713405.1). The COX1 gene sequences of Paragonimus metacercariae from 8 survey sites of Henan Province showed the highest homology (90.0% to 100.0%) with the gene sequence of P. skrjabini (GenBank accession number: AY618798.1), and phylogenetic analysis showed that the Paragonimus in this study was clustered into the same clade with all P. skrjabini and clustered into the same sub-clade with P. skrjabini from Hubei Province (GenBank accession numbers: AY618782.1 and AY618764.1). Conclusions Paragonimus species from freshwater crabs in Henan Province were all characterized as P. skrjabini, and the ITS2 and COX1 gene sequences had the highest homology to those of P. skrjabini from Hubei Province. The results provide insights into study of Paragonimus in Henan Province and China.

Structural Assessment of Chemical Constituent of Sidaguri (Sida rhombifolia Linn) and Its Ability to Inhibit Cyclooxygenase

Objective: To elicit the structure of isolated compounds from roots of sidaguri (Sida rhombifolia Linn). Material and Methods: Several organic standard protocols were involved, including extraction, fractionation, and phytochemical testing. Further spectroscopy methods, FTIR and 1HNMR, were used to determine the predicted structure of molecules, while their ability to inhibit cyclooxygenase (COX 1 and 2) were tested using in vitro method. Results: Overall assessments showed that the structure of the sidaguri is a long chain aliphatic carboxylic acid and identified as Z-3, 6, 6 trimethylhept-2-en-1-ol (T12) and nonanoic (T13). Both isolates significantly inhibit COX-1 and COX-2 non-selectively (the COX-1/COX-2 ratio for T12 was 0.91 and 0.82; while COX-1/COX-2 ratio for T13 was 0.89 and 0.87 at concentrations of 0.05 and 0.025 µg/mL respectively). Conclusion: The active compounds of Sidaguri have antiinflammatory effect by inhibiting COX non-selectively.

New flavonoids and methylchromone isolated from the aerial parts of Baeckea frutescens and their inhibitory activities against cyclooxygenases-1 and -2 / 中国天然药物

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC values ranging from 1.95 to 5.54 μmol·L and ranging from 1.01 to 2.27 μmol·L, respectively.

New flavonoids and methylchromone isolated from the aerial parts of Baeckea frutescens and their inhibitory activities against cyclooxygenases-1 and -2 / 中国天然药物

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC values ranging from 1.95 to 5.54 μmol·L and ranging from 1.01 to 2.27 μmol·L, respectively.

Cyclooxygenase biology in renal function - literature review / Biología de la ciclooxigenasa en la función renal - Revisión de la literatura

Abstract The cyclooxygenase (COX) exists in two main isoforms, COX-1 and COX-2, which are present in the renal system to ensure its homeostasis. However, in different clinical situations, these enzymes can play a physiologic role in maintaining the integrity of this organ, and also be associated with the worsening of tissue injuries/damage. In this sense, an explanation of the true biological function of the isoforms of COX enables a better understanding of the physiology and pathology of the kidney, as well as a better understanding of the consequences of its inhibition by the use of drugs. This review aimed to study the biological role of the COX enzyme in the renal system in different clinical situations.

Resumen La ciclooxigenasa existe en dos isoformas principales: COX-1 y COX-2, estas se encuentran presentes en el sistema renal como parte de su homeostasis. Sin embargo, en algunas situaciones clínicas, las dos enzimas pueden desempeñar un papel en el mantenimiento de la integridad de este órgano, y en otras pueden estar asociadas a la evolución de daños y lesiones en los tejidos. En este sentido, el conocimiento de la verdadera función biológica de las isoformas de la COX permite una mejor comprensión de la fisiología y patología del riñón, así como una mejor comprensión de las consecuencias de su inhibición por el uso de medicamentos. El objetivo de esta revisión es estudiar la función biológica de la enzima COX en el sistema renal en diferentes situaciones clínicas.

Effect of Aging on Related Biological Activity Factors in Gastric Fundic Mucosa in Beagle Dogs / 胃肠病学

Recent studies showed that gastric mucosa was more susceptible to injury by invasion factors with aging, however,the studies were mainly on gastric antral mucosa,fundic mucosa was rarely studied.Aims:To investigate the effect of aging on related biological activity factors in gastric fundic mucosa in beagle dogs.Methods:Nineteen beagle dogs were assigned into younger group (aged 1-5 years),junior elderly group (aged 6-8 years)and senior elderly group (aged≥9 years).The contents of MDA,LPO,MPO in gastric fundic mucosa were determined by TBA method.The contents of PTEN,TE,survivin,caspase-3,caspase-9,ZO-1,CGRP,VEGF,COX-1 and COX-2 were assessed by ELISA.Results:Compared with younger group and junior elderly group,contents of MDA,LPO,MPO,PTEN,TE,ZO-1 ,CGRP,VEGF, COX-1 and COX-2 were significantly increased in senior elderly group (P0.05 ).The content of survivin in junior elderly group and senior elderly group was significantly decreased when compared with younger group (P =0.000 ).Conclusions:Disadvantaging changes of biological activity factors are found in gastric fundic mucosa in elderly beagles dogs,however, gastric mucosal blood flow, mucosa regeneration and epithelial tight junction related biological activity factors are significantly increased in senior elderly beagle dogs,which may be a phenomenon of degeneration-compensation.

Pilot study of the use of Yin Qiao San in children with conventional antipyretic hypersensitivity

BACKGROUND: Children with a diagnosis of cross-reactive hypersensitivity to both paracetamol and nonsteroidal anti-inflammatory drugs are limited in their choice of antipyretics. OBJECTIVE: The aim of this pilot study is to evaluate the feasibility of using a Chinese proprietary medicine, Yin Qiao San (YQS), for fever relief. METHODS: A single centre, open label, prospective clinical trial exploring the tolerability and feasibility of using YQS for fever relief in children who are unable to use conventional antipyretic medications. Children between 1-18 years of age with hypersensitivity to multiple antipyretics were recruited. Eligible participants underwent an oral provocation test with YQS. Children who passed the oral provocation test were instructed to take a prescribed dose of YQS when the temperature was >38.0℃ and continued till the fever settled. Time taken for fever resolution and any adverse events were collected. RESULTS: A total of 21 children, mean age 10.7 years, had a diagnosis of paracetamol and ibuprofen hypersensitivity. All except one patient successfully tolerated an oral challenge of YQS. Of the 88 doses of YQS taken for fever over 38.0℃, 16 (18%) had documented temperature reduction 2 hours after ingestion and 30 (34%) had documented temperature reduction 4 hours after ingestion. There were 2 reports of urticaria after YQS use which were attributed to flare of recurrent spontaneous urticaria during the illness. None of the patients developed symptoms of circulatory compromise or respiratory distress. CONCLUSION: YQS is generally well tolerated in patients with paracetamol and ibuprofen hypersensitivity.

Inhibitory Effects of Epigallocatechin-3-Gallate on Microsomal Cyclooxygenase-1 Activity in Platelets

In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane A2 (TXA2) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration (50 microM) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/TXA2 signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

Study on the beneficial effect of dual peroxisome proliferator-activated receptor agonist WY14643 on vascular endothelium / 中国医师杂志

ObjectiveThe present study aimed to determine whether or not dual paroxysm proliferator-activated receptor (PPAR) agonist,WY14643,improved the dysfunctioned vascular endothelium in hypertension by reducing endothelium-derived contracting factors ( EDCFs ),and to explore the molecular mechanism it was involved in.MethodsIsometric tension in isolated thoracic aortic rings of spontaneously hypertensive rats was recorded.Endothelium-dependent contractions evoked by acetylcholine in the presence of L NAME were reduced by fenofibrate.Cyclooxygenase 1 ( COX1 ) activities were determined by analyzing the peroxidase activity of cyclooxygenase colorimetrically by using ELISA kit.ResultsCompared to the control group,WY14643 significantly decreased the vasoconstriction in aorta of the SHR rats(P=0.014).PPARα antagonist MK866 enhanced the vascular contractility of SHR rats that were incubated with 10.0μmol/L WY14643( P=0.021 ).PPARΥ antagonist GW9662 did not significantly affect the vascular contractility of SHR rats that were incubated with 10.0 μmol/L WY14643( P=0.061 ).The levels of serum PGFlα(P=0.012),2α( P =0.019) and TXB2(P=0.023) in SHR rats incubated with 10.0 μmol/L WY14643 were significantly lower than the control group,respectively.Under the condition of the existence of vascular endothelium,the expression of COX-1 in SHR rats incubated with WY14643 was significantly lower than that in SHR rats incubated without WY14643 (P=0.017).ConclusionsThose data showed that WY14643 reduced the release of EDCFs,it suggests that WY14643 protects against vascular diseases through the PPAR activators in spontaneous hypertension.

Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats

Prostaglandins control osteoblastic and osteoclastic function under physiological or pathological conditions and are important modulators of the bone healing process. The non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and consequently prostaglandins synthesis. Experimental and clinical evidence has indicated a risk for reparative bone formation related to the use of non-selective (COX-1 and COX-2) and COX-2 selective NSAIDs. Ketorolac is a non-selective NSAID which, at low doses, has a preferential COX-1 inhibitory effect and etoricoxib is a new selective COX-2 inhibitor. Although literature data have suggested that ketorolac can interfere negatively with long bone fracture healing, there seems to be no study associating etoricoxib with reparative bone formation. Paracetamol/acetaminophen, one of the first choices for pain control in clinical dentistry, has been considered a weak anti-inflammatory drug, although supposedly capable of inhibiting COX-2 activity in inflammatory sites. OBJECTIVE: The purpose of the present study was to investigate whether paracetamol, ketorolac and etoricoxib can hinder alveolar bone formation, taking the filling of rat extraction socket with newly formed bone as experimental model. MATERIAL AND METHODS: The degree of new bone formation inside the alveolar socket was estimated two weeks after tooth extraction by a differential point-counting method, using an optical microscopy with a digital camera for image capture and histometry software. Differences between groups were analyzed by ANOVA after confirming a normal distribution of sample data. RESULTS AND CONCLUSIONS: Histometric results confirmed that none of the tested drugs had a detrimental effect in the volume fraction of bone trabeculae formed inside the alveolar socket.

Expression of cyclooxygenase-1 and 2 in chronic tonsillitis.

Objectives: Prostaglandins are critical mediators of inflammation and affect both humoral and cell-mediated immune responses. Recent findings show that T and B cells express COX-2 upon activation. The purpose of this study is to investigate the potential occurrence of COX-1 and COX-2 immunoreactivity in cases of chronic tonsillitis and to determine the sites of their expression. In addition, their expression in adult patients is compared with that in child patients. Materials and Methods: Immunohistochemical techniques were used to evaluate the expression of the enzymes COX-1 and COX-2, in chronic tonsillitis tissue specimens from adults (n = 15) and children (n = 15). Results: There was no staining in surface epithelium or reticulated crypt epithelium. COX-1 and COX-2 expressions were observed mainly in the intraepithelial lymphoid cells in reticulated crypt epithelium and subepithelial cells. Also, COX-1 and COX-2 stained cells were found in the germinal center. There was no difference of the expressions of COX-1 and COX-2 among adults and children. The only significant difference noted between the adults and children was that, the adults had rich subepithelial plasma cells. Conclusion: Activated B and T cells express COX-1 and COX-2 in paraffin-embedded tissue sections of chronic tonsillitis. Further studies need to be performed to elucidate expression of COX enzymes and their immunologic role in tonsil diseases. They will play an important role in the treatment of chronic tonsillitis. Additional studies are warranted to study the effects of NSAIDs and selective COX-2 inhibitors in chronic tonsillitis

Expression of Cyclooxygenase-1 in Rat Spinal Cord of a Neuropathic Modal: Sciatic Cryoneurolysis / 中国康复理论与实践

@#ObjectiveTo observe behavioral changes and the dynamic expression of cyclooxygenase-1(COX-1) in the spinal cord of rats after unilateral sciatic cryoneurolysis(SCN).Methods72 male SD rats were randomly divided into 3 groups: normal control group(N, n=6), sham group(S, n=33) and cryoneurolysis group(C, n=33). The mechanical withdrawal threshold and autotomy assession were assessed before and 1, 2, 4 weeks after operation and COX-1 immunohistochemistry was performed on L4-6 spinal cord in 6 rats.ResultsFollowing SCN, rats exhibited significant bilateral tactile hypersensitivity until 4 weeks after operation. Furthermore, we observed autotomy peaked in severity and incidence (in 40% of rats, 1 weeks and 43.8%, 2 weeks ) 1 to 2 weeks after SCN. The COX-1 expression in dorsal horn of the spinal cord in group C was significantly higher than group S 2 and 4 weeks after operation (P<0.05).ConclusionCOX-1 plays an important role in spinal cord pain processing and central sensitization after SCN.

Expression of cyclooxygenase-1 in ovarian cancer and its significance / 军事医学科学院院刊

Objective To explore the expression of cyclooxygenase-1 in ovarian cancer and its significance. Methods Expression of COX-1 and CA125 was detected by immunohistochemistry in 37 cases of ovarian cancer and 31 cases of ovarian cyst. The serum level of COX-1 and CA125 was tested in 40 cases of ovarian cancer and 31 cases of ovarian cyst and 60 healthy volunteers by ELISA. Results The positive expression of COX-1 and CA125 was 78% and 57% in ovarian cancer and 3% and 7% in ovarian cyst,respectively. The expression of COX-1 and CA125 was 65% and 93% at the serum level. Conclusion Expression of COX-1 could act as an auxiliary diagnostic criterion in ovarian carcinoma.

The effects of Gefarnate in treatment of rat model of colitis induced by trinitrobenzene sulphonic acid / 中华消化杂志

Objective To investigate the effects of Gefarnate on expression of myeloperoxidase (MPO),cyelooxygenase-1 (COX-1) and COX-2 in trinitrobenzene sulphonic acid (TNBS) induced experimental colitis in rats and its therapeutic effects on ulcerative colitis. Methods Forty female Sprague-Dawley (SD) rats were randomly divided into 4 groups with 10 each. The rats in group A, B and C were infused with TNBS/alcohol by enema. After the production of colitis, the rats in group A or B were treated daily with 1 ml of normal saline or with 1 ml of 5-ASA (100 mg/kg) by enema,and those in group C were treated daily with 1 ml of Gefarnate by gavage. Group D was served as normal control. After the production of colitis,animals were sacrificed at day 7 and 14 with 5 in each group. The macroscopic changes of the colon were evaluated according to disease activity index (DAD scoring and histological change was assessed by HE staining. MPO activity of the mucosa was detected by biochemical methods. Expressions of COX-1 and COX-2 in tissues were detected by immunohistochemistry. Results Compared with group A, macroscopic and histological scores and MPO activity were significantly decreased in group B and C (P<0.05). The expressions of COX-1 at day 7 and 14 were 1.86±0.51 and 1.96±0.41 in group B, 1.73±0.68 and 1.79±0.6 in group C, 1.91±0.34 and 1.99±0.45 in group D, respectively, which were significantly higher than those in group A (0.87±0.18 and 0.93±0.15, P<0.05). Whereas the expressions of COX-2 at day 7 and 14 were 1.53±0.19 and 0.73±0.15 in group B, 1.73±0.94 and 0.86±0.29 in group C, 0.24±0.18 and 0.18±0. 16 in group D, respectivley, which were significantly lower that those in group A (3.50±0.2;3 and 3.06±0.27). There was a significant difference between group D and group B or C (P<0.05). Conclusions Gefarnate provides a therapeutic effect during TNBS-induced colitis in rats, which is similar to that of 5-ASA. The mechanisms are involved in decreasing the concentration of colonic MPO and regulating the expression of COX-1/COX-2.

Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease / Avaliação da imunoexpressão de COX-1, COX-2 e p53 na doença de Crohn

BACKGROUND: Crohn's disease accompanied by nonspecific or idiopathic ulcerative proctocolitis corresponds to a condition called intestinal inflammatory disease. The immunoexpression of cyclooxygenase 2 (COX-2) in Crohn's disease becomes more marked with progression of the disease and the presence of wild-type p53 suppresses the transcription of COX-2. AIMS: To investigate the immunoexpression of cyclooxygenase 1 (COX-1), COX-2 and p53 in Crohn's ileocolitis and to correlated this expression with clinical and histopathological parameters. METHODS: Forty-five cases of Crohn's disease, 16 cases of actinic colitis (diseased-control group) and 11 cases without a history of intestinal disease (normal control group) were studied. Hematoxylin-eosin-stained sections were submitted to histopathological analysis and the immunohistochemical expression of COX-1, COX-2 and p53 was evaluated by the streptavidin-biotin-peroxidase method. RESULTS: Sixty percent of the Crohn's disease patients were women and 40 percent were men, with 75.5 percent whites and 25.5 percent non-whites. The disease involved the terminal ileum in 44.5 percent of cases, ileum in 33.3 percent, colon in 20 percent and duodenum-ileum in 2.2 percent. A significant association was observed between COX-2 immunoreactivity and age <40 years. Histopathological analysis of Crohn's disease samples showed mild or moderate crypt distortion (57.8 percent and 35.6 percent of cases), atrophy (6.6 percent), mild, moderate and marked chronic inflammation (46.7 percent, 26.7 percent and 20 percent), acute inflammatory activity (93.3 percent), ulceration (24.4 percent), mucin depletion (37.8 percent), Paneth's cells (24.4 percent), intraepithelial lymphocytes (93.3 percent), and subepithelial collagen (6.7 percent). In the CD group, COX-1 immunoreactivity in epithelial and inflammatory cells was observed in 26.7 percent and 22.2 percent of cases, respectively. COX-2 immunoreactivity was detected...

RACIONAL: A doença de Crohn, junto com a colite ulcerativa idiopática ou inespecífica constituem a doença inflamatória intestinal. A imunoexpressão de ciclooxigenase 2 (COX-2) na doença de Crohn acentua-se com a progressão da doença, enquanto que a presença do tipo selvagem de p53 suprime a transcrição de COX-2. OBJETIVOS: Investigar a imunoexpressão de ciclooxigenase 1 (COX-1), COX-2 e p53 na doença de Crohn e correlacionar os achados com parâmetros clínico-histopatológicos. MÉTODOS: Foram estudados 45 casos de doença de Crohn (grupo teste), 16 casos de colite actínica (grupo controle-doente) e 11 casos sem história de doença intestinal (grupo controle normal). A avaliação histopatológica foi feita com lâminas coradas pela hematoxilina-eosina e a imunoexpressão de COX-1, COX-2 e p53 foi avaliada por imunoistoquímica, pelo método da estrepto-avidina-biotina-peroxidase. RESULTADOS: Entre os pacientes com doença de Crohn, 60 por cento eram do sexo feminino e 40 por cento do masculino, 75,5 por cento brancos e 25,5 por cento não-brancos. A doença comprometia o íleo terminal em 44,5 por cento dos casos, íleo em 33,3 por cento, cólon em 20 por cento e duodeno-íleo em 2,2 por cento. Associação significante foi detectada entre a imunoexpressão de COX-2 e pacientes com <40 anos. A histopatologia dos casos de doença de Crohn mostrou distorção críptica em grau leve ou moderado (57,8 por cento e 35,6 por cento dos casos), atrofia (6,6 por cento), inflamação focal, difusa superficial e difusa transmural (46,7 por cento, 26,7 por cento e 20 por cento), inflamação aguda neutrofílica (93,3 por cento), alterações epiteliais: ulceração (24,4 por cento), depleção de mucina (37,8 por cento), células de Paneth (24,4 por cento); alterações epiteliais associadas: linfócitos intra-epiteliais (93,3 por cento) e colágeno subepitelial (6,7 por cento). No grupo doença de Crohn, imunoexpressão de COX-1, em células epiteliais e inflamatórias foi observada em 26,7...

Effect of propyl gallate on cyclooxygenase-1/-2 activity,mRNA and protein expression in murine macrophages / 中国药理学通报

0.05),but enhanced 6-keto-PGF_(1?) synthesis at concentrations of 1,0.5,0.1 and 0.01 ?mol?L~(-1)(P

Expression of Cyclooxygenase 1 and 2 in Laryngeal Squamous Cell Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A large body of evidence from a variety of experimental systems suggests that cyclooxygenase-2 (COX-2) is important in carcinogenesis. This study was to determine whether cyclooxygenase-1 (COX-1) and COX-2 were overexpressed in laryngeal squamous cell carcinoma, and discuss the possible causal role of COX-2 in the laryngeal squamous cell carcinoma formation. MATERIALS AND METHODS: Tissue samples from 21 pateints with laryngeal squamous cell carcinoma were analyzed by immunohistochemical staining. RESULTS: There was an elevation of COX-2 expression in laryngeal squamous cell carcinoma. Normal buccal mucosa biopsies and normal laryngeal epitheliums adjacent to laryngeal cancer showed nondetectable or weak staining for COX-2 protein. There is no difference in the expression of COX -1 in the normal buccal mucosa, normal laryngeal mucosa and laryngeal squamous cell carcinoma. CONCLUSION: There is an overexpression of COX-2, but not COX-1 in laryngeal squamous cell cancer. This may represent a causal role of COX-2 in the formation and proliferation of laryngeal squamous cell carcinoma. There may also be another role of selective COX-2 inhibition for treatment of laryngeal squamous cell carcinoma.

Effects of cyclooxygenase-2 on expression of vascular endothelial growth factor / 中华消化杂志

Objective It has been known that cyclooxygenase-2(COX-2) acts as a tumor promoter in rodent models for colorectal cancer, but its precise role in the processes of carcinogenesis remains unclear. The study was designed to observe the relationship between expression of COX and the expression of vascular endothelial growth factor (VEGF) in the mouse embryo fibroblast (MEF) with knock out of COX-1 gene (COX-1 -/- ) or COX-2 gene (COX-2 -/- ) and wild MEF cells (COX-1 +/+ /COX-2 +/+ ). Methods We cultured the mouse embryo fibroblasts, measured the VEGF levels in the culture medium of these cells using ELISA, and extracted mRNA from these cells to identify the expressions of VEGF isoforms by RT-PCR. Results VEGF level could hardly be measured in the COX 2-deficient cells (COX-2 -/- ), however, the VEGF level was significantly increased in the cells with COX-2 gene (COX-2 +/+ ) and decreased by celecoxib, a COX-2 inhibitor. The level of VEGF was not associated with COX-1 expression. COX-2 inhibited the expressions of three isoforms of VEGF at mRNA level. Conclusions COX-2 plays an important role in the VEGF secretion and synthesis and therefore, it has an effect on the angiogenesis and tumor growth.

Experiment study on the safety of selective COX-2 inhibitor-celecoxib on gastric mucosa / 中华消化杂志

Objective To compare the gastric mucosa damage induced by celecoxib and conventional NSAIDs——indomethacin. Methods NSAIDs induced gastric mucosal damage model in rats was obtained by pouring indomethacin, celecoxib respectively (n=8); After gastric damage induced by means of 100% ethanol, celecoxib were administered by gastric gavage (n=8). Gastric mucosal 6-keto-PGF 1? ,TXB 2 level and lesion index (LI) were measured. Morphological changes of gastric mucosa were assessed under light and scanning electronic microscopy. Results Indomethacin caused obvious gastric damage (LI:13.38?2.06) and a marked reduction of 6-keto-PGF 1? ,TXB 2 level was observed (P