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1.
Parasitol Res ; 119(10): 3233-3241, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32656658

RESUMO

Anisakid nematode larvae occur frequently in the liver of Atlantic cod, but merely few infection data from cod in waters around Greenland exist. The present study reports the occurrence of third-stage anisakid larvae in the livers of 200 Atlantic cod caught on fishing grounds along the West coast of Greenland (fjord systems of Maniitsoq) in May, June, August and September 2017. Classical and molecular helminthological techniques were used to identify the nematodes. A total of 200 cod livers were examined, and 194 were infected with third-stage nematode larvae (overall prevalence of infection 97%) with a mean intensity of 10.3 (range between 1 and 44 parasites per fish). Prevalences recorded were 96% for Anisakis simplex (s.l.), 55% for Pseudoterranova decipiens (s.l.) and 8% for Contracaecum osculatum (s.l.). Sequencing the mtDNA cox2 from 8 out of 23 these latter larvae conferred these to C. osculatum sp. B. A clear seasonal variation was observed, with a rise in A. simplex (s.l.) and P. decipiens (s.l.) occurrence in June and August and a decline in September. The study may serve as a baseline for future investigations using the three anisakids as biological indicators in Greenland waters.


Assuntos
Anisaquíase/epidemiologia , Anisakis/isolamento & purificação , Doenças dos Peixes/parasitologia , Gadus morhua/parasitologia , Animais , Anisakis/classificação , Anisakis/genética , Oceano Atlântico/epidemiologia , Ciclo-Oxigenase 2/genética , DNA Mitocondrial/genética , Groenlândia/epidemiologia , Larva , Fígado/parasitologia
2.
Am J Chin Med ; 48(5): 1091-1102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32668967

RESUMO

Black ginseng (BG), which is ginseng that has been steamed and dried nine times, and its main protopanaxatriol-type ginsenosides Rg4, Rg6, Rh4, and Rg2 have been reported to exhibit various forms of biological activity, including antiseptic, antidiabetic, wound-healing, immune-stimulatory, and anti-oxidant activity. The aim of the this study was to examine the effects of [Formula: see text] (a rare protopanaxatriol-type ginsenoside fraction; Rg2, Rg4, Rg6, Rh1, and Rh4) on heme oxygenase-1 (HO-1) induction and on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-)2 in lipopolysaccharide (LPS)-activated human pulmonary artery endothelial cells (HPAECs). [Formula: see text] was tested to determine its effect on iNOS protein expression and inflammatory markers (interleukin [IL]-1[Formula: see text] and tumor necrosis factor [TNF]-[Formula: see text] in the lung tissue of LPS-treated mice. The results showed that [Formula: see text] induced the expression of HO-1, reduced LPS-activated NF-[Formula: see text]B-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, which contributed to the inhibition of STAT-1 phosphorylation. In particular, [Formula: see text] induced the translocation of Nrf2 from the cytosol to the nucleus by increasing Nrf2-ARE activity and decreased IL-1[Formula: see text] production in LPS-activated HPAECs. This reduction in iNOS/NO expression due to [Formula: see text] was reversed by siHO-1 RNA transfection. In LPS-treated mice, [Formula: see text] significantly reduced lung tissue iNOS protein levels and TNF-[Formula: see text] levels in the bronchoalveolar lavage fluid. In conclusion, these findings indicate that [Formula: see text] has a critical anti-inflammatory effect due to its ability to regulate iNOS via the inhibition of p-STAT-1 and NF-[Formula: see text]B, and thus it may be suitable for the treatment of inflammatory disease.


Assuntos
Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Inflamação/genética , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Panax/química , Fator de Transcrição STAT1/metabolismo , Animais , Anti-Inflamatórios , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Ginsenosídeos/isolamento & purificação , Heme Oxigenase-1/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Luciferases/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Fitoterapia
3.
Chem Biol Interact ; 325: 109088, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360554

RESUMO

Osteoarthritis (OA) is one of the most common degenerative joint diseases in aging people. The activation of chondrocytes and their dysregulation are closely related to the pathogenesis of OA. GPR55 is an unique orphan G-receptor which binds to cannabinoids. In this study, we explored the role of GPR55 in advanced glycation end productions (AGEs)- induced chondrocytes activation in cultured cells. We showed that AGEs dose dependently induced GPR55 expression in ATDC5 chondrocytes. The blockage of GPR55 by its newly discovered antagonist-CID16020046 mitigated AGEs- induced increase in cellular ROS and decrease in antioxidant NRF2. Moreover, CID16020046 showed a dose-response suppressive effect on AGEs- induced expression of the major inflammatory mediators, including COX-2 and iNOS, and the production of NO and PGE2. CID16020046 also dose responsively inhibited AGEs- induced key effectors of cartilage degradation such as MMP-3 and MMP-13. In consequence, CID16020046 showed robust inhibition on AGEs- induced type II collagen degradation. Mechanistically, our data demonstrated that CID16020046 mediated GPR55 blockage ameliorated AGEs- induced NF-κB activation as revealed by its inhibition on IκBα, nuclear p65 translocation and NF-κB promoter activity. Collectively, our study demonstrates that GPR55 signaling mediates AGEs- induced chondrocyte activation, and the targeted blockage of GPR55 pathway could be therapeutic choice in the treatment of osteoarthritis.


Assuntos
Compostos Azabicíclicos/farmacologia , Benzoatos/farmacologia , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Produtos Finais de Glicação Avançada/farmacologia , Receptores de Canabinoides/metabolismo , Linhagem Celular , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Ciclo-Oxigenase 2/genética , Dinoprostona/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Proteólise/efeitos dos fármacos
4.
Prostate ; 80(10): 731-741, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32356572

RESUMO

BACKGROUND: Male lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells. METHODS: Immunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1ß and TGF-ß1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN. RESULTS: OPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-ß1 stimulated OPN secretion by NHPrE-1 cells and both IL-1ß and TGF-ß1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines. CONCLUSIONS: OPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.


Assuntos
Osteopontina/biossíntese , Hiperplasia Prostática/metabolismo , Quimiocinas CXC/biossíntese , Quimiocinas CXC/genética , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/genética , Humanos , Imuno-Histoquímica , Interleucina-6/biossíntese , Interleucina-6/genética , Masculino , Osteopontina/genética , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Células Estromais/metabolismo , Células Estromais/patologia
5.
PLoS One ; 15(5): e0232930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401801

RESUMO

INTRODUCTION: Probiotics are suggested to prevent colorectal cancer (CRC). This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo. MATERIALS AND METHODS: Anticancer effects of the following potential probiotic groups were investigated in LS174T cancer cells compared to IEC-18 normal cells. 1. a single strain of Bifidobacterium. breve, 2. a single strain of Lactobacillus. reuteri, 3. a cocktail of 5 strains of Lactobacilli (LC), 4. a cocktail of 5 strains of Bifidobacteria (BC), 5. a cocktail of 10 strains from Lactobacillus and Bifidobacterium (L+B). Apoptosis rate, EGFR, HER-2 and PTGS-2 (COX-2 protein) expression levels were assessed as metrics of evaluating anticancer properties. Effect of BC, as the most effective group in vitro, was further assessed in mice models. RESULTS: BC induced ~21% and only ~3% apoptosis among LS174T and IEC-18 cells respectively. BC decreased the expression of EGFR by 4.4 folds, HER-2 by 6.7 folds, and PTGS-2 by 20 folds among the LS174T cells. In all these cases, BC did not interfere significantly with the expression of the genes in IEC-18 cells. This cocktail has caused only 1.1 folds decrease, 1.8 folds increase and 1.7 folds decrease in EGFR, HER-2 and PTGS-2 expression, respectively. Western blot analysis confirmed these results in the protein level. BC significantly ameliorated the disease activity index, restored colon length, inhibited the increase in incidence and progress of tumors to higher stages and grades. CONCLUSIONS: BC was the most efficient treatment in this study. It had considerable "protective" anti-cancer properties and concomitantly down regulated EGFR, HER-2 and PTGS-2 (COX-2), while having significant anti-CRC effects on CRC mice models. In general, this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC.


Assuntos
Bifidobacterium/fisiologia , Neoplasias Colorretais/dietoterapia , Ciclo-Oxigenase 2/genética , Probióticos/administração & dosagem , Receptor ErbB-2/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Probióticos/farmacologia , Receptor ErbB-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Nat Commun ; 11(1): 2358, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398649

RESUMO

Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD.


Assuntos
Doença de Alzheimer/imunologia , Anti-Inflamatórios/farmacologia , Encéfalo/imunologia , Microglia/imunologia , Esfingosina/análogos & derivados , Acetilcoenzima A/metabolismo , Acetilação , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Anti-Inflamatórios/uso terapêutico , Encéfalo/patologia , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/patologia , Mutagênese , Neurônios , Fagocitose/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Presenilina-1/genética , Cultura Primária de Células , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Serina/metabolismo , Esfingosina/metabolismo
7.
J Toxicol Sci ; 45(4): 227-236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32238697

RESUMO

A growing body of experimental evidence strongly suggests that cannabidiolic acid (CBDA), a major component of the fiber-type cannabis plant, exerts a variety of biological activities. We have reported that CBDA can abrogate cyclooxygenase-2 (COX-2) expression and its enzymatic activity. It is established that aberrant expression of COX-2 correlates with the degree of malignancy in breast cancer. Although the reduction of COX-2 expression by CBDA offers an attractive medicinal application, the molecular mechanisms underlying these effects have not fully been established. It has been reported that COX-2 expression is positively controlled by peroxisome proliferator-activated receptor ß/δ (PPARß/δ) in some cancerous cells, although there is "no" modulatory element for PPARß/δ on the COX-2 promoter. No previous studies have examined whether an interaction between PPARß/δ-mediated signaling and COX-2 expression exists in MDA-MB-231 cells. We confirmed, for the first time, that COX-2 expression is positively modulated by PPARß/δ-mediated signaling in MDA-MB-231 cells. CBDA inhibits PPARß/δ-mediated transcriptional activation stimulated by the PPARß/δ-specific agonist, GW501516. Furthermore, the disappearance of cellular actin stress fibers, a hallmark of PPARß/δ and COX-2 pathway activation, as evoked by the GW501516, was effectively reversed by CBDA. Activator protein-1 (AP-1)-driven transcriptional activity directly involved in the regulation of COX-2 was abrogated by the PPARß/δ-specific inverse agonists (GSK0660/ST-247). Thus, it is implicated that there is positive interaction between PPARß/δ and AP-1 in regulation of COX-2. These data support the concept that CBDA is a functional down-regulator of COX-2 through the abrogation of PPARß/δ-related signaling, at least in part, in MDA-MB-231 cells.


Assuntos
Neoplasias da Mama/enzimologia , Canabinoides/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Expressão Gênica/genética , PPAR delta/fisiologia , Feminino , Humanos , PPAR delta/agonistas , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Sulfonas/farmacologia , Tiazóis/farmacologia , Tiofenos/farmacologia , Fator de Transcrição AP-1/fisiologia , Células Tumorais Cultivadas
8.
PLoS One ; 15(3): e0230272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168360

RESUMO

Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) of prostate and urinary bladder are highly invasive and metastatic tumors of closely neighbored organs. Cell lines are valuable tools to investigate tumor mechanisms and therapeutic approaches in vitro. PAC in dogs is infrequent, difficult to differentiate from TCC and usually characterized by poor prognosis, enhancing the value of the few available cell lines. However, as cell lines adapt to culturing conditions, a thorough characterization, ideally compared to original tissue, is indispensable. Herein, six canine PAC cell lines and three TCC cell lines were profiled by immunophenotype in comparison to respective original tumor tissues. Three of the six PAC cell lines were derived from primary tumor and metastases of the same patient. Further, two of the three TCC cell lines were derived from TCCs invading into or originating from the prostate. Cell biologic parameters as doubling times and chemoresistances to commonly used drugs in cancer treatment (doxorubicin, carboplatin and meloxicam) were assessed. All cell lines were immunohistochemically close to the respective original tissue. Compared to primary tumor cell lines, metastasis-derived cell lines were more chemoresistant to doxorubicin, but equally susceptive to carboplatin treatment. Two cell lines were multiresistant. COX-2 enzyme activity was demonstrated in all cell lines. However, meloxicam inhibited prostaglandin E2 production in only seven of nine cell lines and did neither influence metabolic activity, nor proliferation. The characterized nine cell lines represent excellent tools to investigate PAC as well as TCC in prostate and urinary bladder of the dog. Furthermore, the profiled paired cell lines from PAC primary tumor and metastasis provide the unique opportunity to investigate metastasis-associated changes PAC cells undergo in tumor progression. The combination of nine differently chemoresistant PAC and TCC cell lines resembles the heterogeneity of canine lower urinary tract cancer.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células de Transição/patologia , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Animais , Carboplatina/farmacologia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/imunologia , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/imunologia , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Doenças do Cão/tratamento farmacológico , Doenças do Cão/genética , Doenças do Cão/imunologia , Doenças do Cão/patologia , Cães , Doxorrubicina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imunofenotipagem , Masculino , Meloxicam/farmacologia , Metástase Neoplásica , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia
9.
Life Sci ; 248: 117464, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097667

RESUMO

AIMS: The present study was carried out to investigate the influences of Selenium/Zinc-Enriched probiotics (SeZnP) on growth performance, serum enzyme activity, antioxidant capability, inflammatory factors and gene expression associated with Wistar rats inflated under high ambient thermal-stress. MAIN METHODS: Sixty male rates with six-weeks of age were randomly allocated into five groups (12 per group) and fed basal diet (Control), basal diet supplemented with probiotics (P), Zinc-Enriched probiotics (ZnP, 100 mg/L), Selenium-Enriched Probiotics (SeP, 0.3 mg/L) and Selenium/Zinc-Enriched probiotics (SeZnP, 0.3 mg + 100 mg/L). The experiment lasted 30 days. Blood and Tissues samples were taken to investigate serum enzyme activity, antioxidants capability and inflammatory factors by using of commercial kits and antioxidant, heat shock and inflammatory related molecules expressions were determined by qRT-PCR. KEY FINDINGS: Data analysis revealed that thermal stress significantly increased the level of Aspartate-aminotransferase, Alanine-aminotransferase, Lactate-dehydrogenase, Creatine-kinase, blood urea nitrogen, Creatinine and Alkaline phosphatase compared to P, ZnP, SeP or SeZnP groups (P < 0.01). However, supplementation of ZnP, SeP, and SeZnP significantly enhanced glutathione content, glutathione-peroxidase & superoxide-dismutase activity, and decreased malondialdehyde content (P < 0.05). Moreover, the concentration of IL-2, IL-6 and IL-8 were significantly increased while IL-10 was significantly decreased (P < 0.05). Furthermore, the expression of GPx1 and SOD1 genes were significantly increased, but COX-2, iNOS, HSP70 and 90 mRNA levels were significantly decreased (P < 0.05). Finally, the highest influence of the mentioned parameters was observed in SeZnP supplemented group. SIGNIFICANCE: Our study suggests that SeZnP supplementation serves as possible and best nutritive than ZnP or SeP for Wistar rats raising under high ambient temperature.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Probióticos/administração & dosagem , Selênio/administração & dosagem , Zinco/administração & dosagem , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Nitrogênio da Ureia Sanguínea , Creatina Quinase/genética , Creatina Quinase/metabolismo , Creatinina/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Resposta ao Choque Térmico/genética , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
10.
J Gastroenterol Hepatol ; 35(5): 896-904, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32064683

RESUMO

BACKGROUND AND AIM: The prophylactic effect of nonselective nonsteroidal anti-inflammatory drugs on post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis has been observed for a long time. However, whether the selective nonsteroidal anti-inflammatory drugs possess similar abilities and the mechanisms by which nonsteroidal anti-inflammatory drugs work remain unclear. The present study aimed to determine the protective effects of nonsteroidal anti-inflammatory drugs on post-ERCP pancreatitis in a rat model and examine underlying mechanisms. METHODS: Thirty-two female rats were equally and randomly divided into four groups: the sham group, post-ERCP pancreatitis model group, indomethacin-pretreated group, and parecoxib-pretreated group. Indomethacin or parecoxib was delivered 30 min prior to surgery; 24 h after post-ERCP pancreatitis establishment, the rats were sacrificed. Serum amylase and lipase activities, inflammatory cytokine release, pancreatic histopathological scores, neutrophil infiltration, and the expression pattern cyclooxygenase at the protein level and pancreatic apoptosis were quantified and analyzed. RESULTS: Both indomethacin and parecoxib inhibited the activities of serum amylase and lipase and reduced the severity of pancreatic histopathology. Mechanistically, both drugs decreased the expression level of cyclooxygenase 2; however, they had no influence on the cyclooxygenase 1 protein level. Moreover, they reduced inflammatory cytokine release, neutrophil infiltration into the pancreas, and NF-κB p65 activation. Notably, we found that apoptotic cells in the pancreas were remarkably diminished after the administration of both nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Both selective and nonselective nonsteroidal anti-inflammatory drugs exert protective effects against post-ERCP pancreatitis by restraining inflammation and reducing acinar cell apoptosis through the inhibition of cyclooxygenase 2.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Apoptose/efeitos dos fármacos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Indometacina/administração & dosagem , Isoxazóis/administração & dosagem , Pancreatite/etiologia , Pancreatite/prevenção & controle , Células Acinares/patologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2 , Feminino , Expressão Gênica/efeitos dos fármacos , Pancreatite/patologia , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença
11.
Med Sci Monit ; 26: e920211, 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927559

RESUMO

BACKGROUND The aim of this study was to investigate the mechanisms underlying the potential effects of hydrogen-rich water (HW) on articular cartilage in a rat osteoarthritis (OA) model. MATERIAL AND METHODS A rat model of OA was established using the modified Hulth method, and rats were forced to exercise for 30 min every day 1 week after surgery for 7 weeks. Mankin's method was used to score the severity of OA. The animals were assigned into the OA group, OA+HW group, and sham operation group. After 8 weeks, the animals in the OA group had a Mankin score >8 points, and HW was administered into the knee joint. After 2 weeks of treatment, articular cartilage was obtained for pathological examination, consisting of hematoxylin and eosin, toluidine blue, and Hoechst staining, as well as quantitative real-time PCR and Western blot analyses. This combination of pharmacological and molecular biological analyses was performed to examine the mechanism underlying the protective effect of HW on articular cartilage. RESULTS The antioxidant effects of HW suppressed oxidative damage, which may have aided the inhibition of ECM-degrading enzymes (MMP3, MMP13, ADAMT4, and ADAMT5), the upregulation of Col II and aggrecan expression, and the downregulation of COX-2, iNOS, and NO expression. The results of HE staining indicated intra-articular treatment of HW attenuated cartilage degradation. However, Hoechst staining in the OA group indicated the nuclei of the fragmented chondrocytes were condensed compared to the sham operation group, and this effect was inhibited by HW. CONCLUSIONS HW showed a protective effect against the progression of OA in an animal model, which may have been mediated by its anti-oxidant and anti-apoptotic activities.


Assuntos
Apoptose/efeitos dos fármacos , Cartilagem Articular/patologia , Matriz Extracelular/metabolismo , Hidrogênio/uso terapêutico , Osteoartrite/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Água/farmacologia , Proteínas ADAM/metabolismo , Agrecanas/metabolismo , Animais , Cartilagem Articular/efeitos dos fármacos , Caspase 3/metabolismo , Colágeno Tipo II/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/patologia , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo
12.
Am J Physiol Gastrointest Liver Physiol ; 318(3): G375-G389, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31928220

RESUMO

Mixed acidic-alkaline refluxate is a major pathogenic factor in chronic esophagitis progressing to Barrett's esophagus (BE). We hypothesized that epidermal growth factor (EGF) can interact with COX-2 and peroxisome proliferator-activated receptor-γ (PPARγ) in rats surgically prepared with esophagogastroduodenal anastomosis (EGDA) with healthy or removed salivary glands to deplete salivary EGF. EGDA rats were treated with 1) vehicle, 2) EGF or PPARγ agonist pioglitazone with or without EGFR kinase inhibitor tyrphostin A46, EGF or PPARγ antagonist GW9662 respectively, 3) ranitidine or pantoprazole, and 4) the selective COX-2 inhibitor celecoxib combined with pioglitazone. At 3 mo, the esophageal damage and the esophageal blood flow (EBF) were determined, the mucosal expression of EGF, EGFR, COX-2, TNFα, and PPARγ mRNA and phospho-EGFR/EGFR protein was analyzed. All EGDA rats developed chronic esophagitis, esophageal ulcerations, and intestinal metaplasia followed by a fall in the EBF, an increase in the plasma of IL-1ß, TNFα, and mucosal PGE2 content, the overexpression of COX-2-, and EGF-EGFR mRNAs, and proteins, and these effects were aggravated by EGF and attenuated by pioglitazone. The rise in EGF and COX-2 mRNA was inhibited by pioglitazone but reversed by pioglitazone cotreated with GW9662. We conclude that 1) EGF can interact with PG/COX-2 and the PPARγ system in the mechanism of chronic esophagitis; 2) the deleterious effect of EGF involves an impairment of EBF and the overexpression of COX-2 and EGFR, and 3) agonists of PPARγ and inhibitors of EGFR may be useful in the treatment of chronic esophagitis progressing to BE.NEW & NOTEWORTHY Rats with EGDA exhibited chronic esophagitis accompanied by a fall in EBF and an increase in mucosal expression of mRNAs for EGF, COX-2, and TNFα, and these effects were exacerbated by exogenous EGF and reduced by removal of a major source of endogenous EGF with salivectomy or concurrent treatment with tyrphostin A46 or pioglitazone combined with EGF. Beneficial effects of salivectomy in an experimental model of BE were counteracted by PPARγ antagonist, whereas selective COX-2 inhibitor celecoxib synergistically with pioglitazone reduced severity of esophageal damage and protected esophageal mucosa from reflux. We propose the cross talk among EGF/EGFR, PG/COX-2, and proinflammatory cytokines with PPARγ pathway in the mechanism of pathogenesis of chronic esophagitis progressing to BE and EAC.


Assuntos
Esôfago de Barrett/metabolismo , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Mucosa Esofágica/metabolismo , Esofagite/metabolismo , PPAR gama/metabolismo , Animais , Esôfago de Barrett/tratamento farmacológico , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/antagonistas & inibidores , Fator de Crescimento Epidérmico/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/patologia , Esofagite/tratamento farmacológico , Esofagite/genética , Esofagite/patologia , Interleucina-1beta/metabolismo , Masculino , PPAR gama/agonistas , PPAR gama/genética , Pioglitazona/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Ratos Wistar , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
13.
Adv Exp Med Biol ; 1232: 277-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893421

RESUMO

Acidification of the cellular microenvironment is found in different pathological states such as inflammation, ischemia and in solid tumors. It can affect cell function and phenotype, and by this aggravate the pathological process. Epithelial cells are a relevant functional part in several normal organs as well as in tumors and will thus be challenged by the acidic extracellular pH (acidosis). Therefore, the impact of acidosis on the expression of different inflammatory mediators (MCP-1, IL-6, osteopontin, iNOS, TNF-α, and COX-2), as well as the role of different signaling pathways regulating the expression, was studied in epithelial normal rat kidney cells (NRK-52E). Acidosis led to an increase in TNF-α expression but a down-regulation of MCP-1, iNOS and COX-2. Expression of IL-6 was only slightly modulated, while osteopontin was not regulated at all. Since acidosis activates ERK1/2 and p38 signaling in NRK-52E cells, the impact of MAP kinase signaling pathways on the expression of the inflammatory markers was analyzed. At normal pH, blocking ERK1/2 or p38 decreased the level of MCP-1, iNOS and partly TNF-α. However, the effect of acidosis on the expression of inflammatory mediators was not affected by inhibition of the MAP kinase pathways. In conclusion, our results show that an acidic microenvironment affects the transcriptional program of epithelial cells. Low pH mostly reduced the expression of pathological relevant genes and might thus repress inflammatory processes induced by epithelial cells.


Assuntos
Acidose , Células Epiteliais , Regulação da Expressão Gênica , Mediadores da Inflamação , Proteínas Quinases p38 Ativadas por Mitógeno , Acidose/metabolismo , Animais , Linhagem Celular , Quimiocina CCL2/genética , Ciclo-Oxigenase 2/genética , Células Epiteliais/metabolismo , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Óxido Nítrico Sintase Tipo II/genética , Ratos , Fator de Necrose Tumoral alfa/genética
14.
J Biochem Mol Toxicol ; 34(2): e22422, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31729780

RESUMO

M1 macrophages serve one edge as proinflammatory and M2 macrophages serve the other edge as an anti-inflammatory macrophage. It appears that a related "switch" in macrophage morphology may also happen in the course of atherosclerosis, which has not yet been elucidated. An atherogenic diet (AD) was given to rats, and induction of macrophage differentiation and the nuclear localization of nuclear factor-kappa B (NFκB) were investigated by Western blot and immunofluorescence. Chemokines were analyzed using an antibody array with 32 target proteins. M2 macrophage transformation was confirmed in diosgenin-treated aorta by immunofluorescence and was validated in vitro using THP-1 cells. MAC387 (macrophage marker) and NFκBp65 (inflammatory hub) were upregulated in oxidatively-modified low-density lipoprotein (OxyLDL) and AD-induced condition. Macrophage differentiation, which induced the formation of inflammatory mediators, was not significantly suppressed by the inhibition of NFκB using dexamethasone. M1 macrophage polarization was identified in OxyLDL-induced monocytes, which are proinflammatory in nature, whereas M2 macrophage polarization was noticed in diosgenin-treated monocytes, which exhibit anti-inflammatory properties. M1-and M2-specific chemokines were analyzed using chemokine antibody array. Furthermore, the expression of proinflammatory macrophage (M1) was noticed in AD-induced aorta and anti-inflammatory macrophage (M2) was observed in diosgenin-treated aorta. This is the first report where, unifying the mechanism of diosgenin as aan nti-atherosclerotic and the expression of M1 and M2 specific chemokines is shown by downregulating NFκB and not by preventing the differentiation of monocyte into a macrophage, but by allowing macrophage to differentiate into M2, which aids in preventing the atherosclerotic progression.


Assuntos
Aorta/metabolismo , Aterosclerose/metabolismo , Polaridade Celular , Citocinas/metabolismo , Diosgenina/farmacologia , Macrófagos/metabolismo , Extratos Vegetais/farmacologia , Fator de Transcrição RelA/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Antígenos CD36/genética , Antígenos CD36/metabolismo , Diferenciação Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dexametasona/farmacologia , Dieta Aterogênica/efeitos adversos , Dioscorea/química , Diosgenina/uso terapêutico , Humanos , Lipoproteínas LDL/farmacologia , Masculino , Monócitos/metabolismo , Extratos Vegetais/uso terapêutico , Ratos , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/genética
15.
Chem Biol Interact ; 317: 108903, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31811862

RESUMO

The snake venom miotoxin (MT)-III is a group IIA secreted phospholipase A2 (sPLA2) with pro-inflammatory activities. Previous studies have demonstrated that MT-III has the ability to stimulate macrophages to release inflammatory lipid mediators derived from arachidonic acid metabolism. Among them, we highlight prostaglandin (PG)E2 produced by the cyclooxygenase (COX)-2 pathway, through activation of nuclear factor (NF)-κB. However, the mechanisms coordinating this process are not fully understood. This study investigates the regulatory mechanisms exerted by other groups of bioactive eicosanoids derived from 12-lipoxygenase (12-LO), in particular 12-hydroxyeicosatetraenoic (12-HETE), on group IIA sPLA2-induced (i) PGE2 release, (ii) COX-2 expression, and (iii) activation of signaling pathways p38 mitogen-activated protein kinases(p38MAPK), protein C kinase (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-κB. Stimulation of macrophages with group IIA sPLA2 resulted in release of 12-HETE without modification of 12-LO protein levels. Pre-treatment of these cells with baicalein, a 12-LO inhibitor, decreased the sPLA2-induced PGE2 production, significantly reduced COX-2 expression, and inhibited sPLA2-induced ERK; however, it did not affect p38MAPK or PKC phosphorylation. In turn, sPLA2-induced PGE2 release and COX-2 expression, but not NF-κB activation, was attenuated by pre-treating macrophages with PD98059 an inhibitor of ERK1/2. These results suggest that, in macrophages, group IIA sPLA2-induced PGE2 release and COX-2 protein expression are distinctly mediated through 12-HETE followed by ERK1/2 pathway activation, independently of NF-κB activation. These findings highlight an as yet undescribed mechanism by which 12-HETE regulates one of the distinct signaling pathways for snake venom group IIA sPLA2-induced PGE2 release and COX-2 expression in macrophages.


Assuntos
Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Fosfolipases A2 do Grupo II/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Venenos de Serpentes/enzimologia , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/genética , Animais , Células Cultivadas , Ciclo-Oxigenase 2/genética , Dinoprostona/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos
16.
Arch Physiol Biochem ; 126(1): 74-81, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30320514

RESUMO

This study evaluated the anti-inflammatory potential of a 40% prethanol extract of Trifolium pratense leaves (40% PeTP) using in vitro (RAW264.7 cells) and in vivo (carrageenan-induced inflammation model) experiments. Pretreatment with 40% PeTP significantly inhibited the LPS-induced expression of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines, including tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in RAW264.7 cells, without inducing cytotoxicity. The inhibitory effects of 40% PeTP are mediated through suppression of the nuclear translocation of nuclear factor (NF)-κB and the phosphorylation of mitogen-activated protein kinases (MAPKs). Oral administration of 40% PeTP at 50, 100, and 200 mg/kg of body weight suppressed carrageenan-induced oedema in a dose-dependent manner. Collectively, our results suggested that 40% PeTP exerts potential anti-inflammatory effects by suppressing the activation of the NF-κB and MAPK pathways in vitro, and by reducing carrageenan-induced paw oedema in vivo.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/genética , NF-kappa B/genética , Extratos Vegetais/farmacologia , Trifolium/química , Administração Oral , Animais , Carragenina/administração & dosagem , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Modelos Animais de Doenças , Esquema de Medicação , Edema/induzido quimicamente , Edema/genética , Edema/patologia , Regulação da Expressão Gênica , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Folhas de Planta/química , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
Am J Physiol Cell Physiol ; 318(1): C73-C82, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577514

RESUMO

Our objective was to investigate the role of primary cilia in low-magnitude, high-frequency vibration (LMHFV) treatment of MC3T3-E1 osteoblasts (OBs). We used chloral hydrate (CH), which has a well-characterized function in chemically removing primary cilia, to elucidate the role of primary cilia in LMHFV-induced OB osteogenic responses through cell viability assay, Western blot analysis, real-time quantitative RT-PCR, and histochemical staining methods. We observed a significant, 30% decrease in the number of MC3T3-E1 OBs with primary cilia (reduced from 64.3 ± 5%) and an approximately 50% reduction in length of primary cilia (reduced from 3 ± 0.8 µm) after LMHFV stimulation. LMHFV stimulation upregulated protein expression of the bone matrix markers collagen 1 (COL-1), osteopontin (OPN), and osteoclacin(OCN) in MC3T3-E1 OBs, indicating that LMHFV induces osteogenesis. High-concentration or long-duration CH exposure resulted in inhibition of MC3T3-E1 OB survival. In addition, Western blot analysis and RT-PCR revealed that CH treatment prevented LMHFV-induced osteogenesis. Furthermore, decreased alkaline phosphate activity, reduced OB differentiation, mineralization, and maturation were observed in CH-pretreated and LMHFV-treated OBs. We showed that LMHFV induces morphological changes in primary cilia that may fine-tune their mechanosensitivity. In addition, we demonstrated the significant inhibition by CH of LMHFV-induced OB mineralization, maturation, and differentiation, which might reveal the critical role of primary cilia in the process.


Assuntos
Diferenciação Celular , Cílios/metabolismo , Mecanotransdução Celular , Osteoblastos/metabolismo , Osteogênese , Vibração , Células 3T3 , Animais , Diferenciação Celular/genética , Hidrato de Cloral/toxicidade , Cílios/efeitos dos fármacos , Cílios/patologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação da Expressão Gênica , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/metabolismo , Fatores de Tempo
18.
Mol Carcinog ; 59(3): 265-280, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31867776

RESUMO

Nasopharyngeal carcinoma (NPC) has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. We have previously shown that high cyclooxygenase-2 (COX-2) expression is associated with a poor prognosis of patients with NPC and inhibits chemotherapy-induced senescence in NPC cells. In this study, we found that COX-2 was upregulated in cancer-associated fibroblasts (CAFs) derived from NPC by RNA-Seq. Furthermore, elevated COX-2 expression in CAF was detected in NPC patients with poor survival and distant metastasis by using immunohistochemistry. Then, we identified that COX-2 is highly expressed in CAF at the distant metastasis site in seven paired NPC patients. High expression of COX-2 and secretion of prostaglandin E2, a major product catalyzed by COX-2 in fibroblasts, promotes migration and invasiveness of NPC cells in vitro. On the contrary, inhibition of COX-2 has the opposite effect in vitro as well as in the COX-2-/- mouse with the lung metastasis model in vivo. Mechanistically, we discovered that COX-2 elevates tumor necrosis factor-α expression in CAF to promote NPC cell migration and invasiveness. Overall, our results identified a novel target in CAF promoting NPC metastasis. Our findings suggested that high expression of COX-2 in CAF may serve as a new prognostic indicator for NPC metastasis and provide the possibility of targeting CAF for treating advanced NPC.


Assuntos
Fibroblastos Associados a Câncer/patologia , Ciclo-Oxigenase 2/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Regulação para Cima
19.
Biosci Biotechnol Biochem ; 84(4): 757-763, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31868102

RESUMO

Prostaglandin E2 (PGE2), which is a potent pro-inflammatory lipid mediator, is biosynthesized from arachidonic acid by cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Non-steroidal anti-inflammatory drugs (NSAIDs) are used clinically as COX inhibitors, but they have gastrointestinal and cardiovascular side-effects. Thus, the terminal enzyme mPGES-1 holds promise as the next therapeutic target. In this study, we found that the ellagitannins granatin A and granatin B isolated from pomegranate leaves, and geraniin, which is their structural analog, selectively suppressed mPGES-1 expression without affecting COX-2 in non-small cell lung carcinoma A549 cells. The ellagitannins also down-regulated tumor necrosis factor α, inducible nitric oxide synthase, and anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2, and induced A549 cells to undergo apoptosis. These findings indicate that the ellagitannins have anti-inflammatory and anti-carcinogenic effects, due to their specific suppression of mPGES-1.Abbreviations: Bcl-2: B-cell chronic lymphocytic leukemia/lymphoma 2; COX: cyclooxygenase; CRE: cAMP response element; DHHDP: dehydrohexahydroxydiphenoyl; Et2O: diethyl ether; EtOAc: ethyl acetate; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; iNOS: inducible nitric oxide synthase; mPGES-1: microsomal prostaglandin E synthase-1; n-BuOH: water-saturated n-butanol; NSAIDs: non-steroidal anti-inflammatory drugs; NF-κB: nuclear factor-κB; PG: prostaglandin; TNF: tumor necrosis factor; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.


Assuntos
Apoptose/efeitos dos fármacos , Taninos Hidrolisáveis/farmacologia , Neoplasias Pulmonares/patologia , Folhas de Planta/química , Romã (Fruta)/química , Prostaglandina-E Sintases/antagonistas & inibidores , Células A549 , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Humanos , Prostaglandina-E Sintases/genética , Prostaglandina-E Sintases/metabolismo , RNA Mensageiro/genética
20.
Mater Sci Eng C Mater Biol Appl ; 107: 110254, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761216

RESUMO

Polymorphous light eruption (PLE) is one of the acquired idiopathic photodermatosis mainly induced by immoderate UV radiation. In order to realize UV protection and medicine administration simultaneously for polymorphous light eruption protection and therapy, Acetyl-11-keto-ß-boswellic acid (AKBA) loaded Zinc Oxide (ZnO) nanoparticles of which drug release behavior is UV-controlled has been successfully synthesized. Such nanoparticles can not only reflect UV but also transfer the energy to release AKBA which presents an excellent antioxidant and anti-inflammatory effects. In addition, they are biocompatible to HaCaT cells. As a result, they have a great potential in combining UV protection and medicine administration simultaneously for PLE protection and therapy.


Assuntos
Nanopartículas/química , Triterpenos/química , Raios Ultravioleta , Óxido de Zinco/química , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Nanopartículas/toxicidade , Transtornos de Fotossensibilidade/patologia , Transtornos de Fotossensibilidade/prevenção & controle , Espécies Reativas de Oxigênio , Triterpenos/metabolismo , Triterpenos/farmacologia
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