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PURPOSE: The effect of urotensin II (U-II), a powerful endogenous vasoconstrictor substance, on the immune system and its mediators is very important. It was herein aimed to demonstrate the possible relationship between the calcineurin/nuclear factor of activated T-cells cytoplasmic 1/interleukin-2 (CaN/NFATc/IL-2) pathway and urotensin receptors (UTRs) in inflammatory response due to lipopolysaccharide (LPS). METHODS: An LPS-induced inflammation model was used on the human umbilical vein endothelial cells (HUVEC) cell line and drugs were applied accordingly, forming the following groups: Control Group, LPS Group, Agonist Group (10-8 âM U-II), Antagonist Group (10-6 âM palosuran), Tacrolimus (TAC) Group (10 âng/mL FK-506), Agonist â+ âTAC Group, and Antagonist â+ âTAC Group. Gene expression analyses were performed using real-time polymerase chain reaction (RT-PCR). RESULTS: In the analysis of the cell viability at 48 and 72 âh, there was a decrease in the Agonist Group, while in the Agonist â+ âTAC Group, the cell viability increased. In the Antagonist Group, cell viability was maintained when compared to the LPS Group, while in the TAC Group, this effect was reduced. The mRNA expression levels of UTR, CaN, NFATc, IL-2 receptor (IL-2R), IL-6 and nuclear factor kappa B (NF-κB) were higher in the LPS Group than in the Control Group, and even the UTR, CaN, NFATc, IL-2R were higher with agonist administration. This effect of the agonist was shown to be completely mitigated in the presence of the CaN inhibitor. CONCLUSION: U-II and its receptors can perform key functions regarding the endothelial cell damage via the CaN/NFATc/IL-2 pathway.
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Interleucina-2 , Lipopolisacáridos , Humanos , Lipopolisacáridos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Interleucina-2/metabolismo , Interleucina-2/farmacología , Calcineurina/metabolismo , Calcineurina/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Objectives: Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. Materials and Methods: 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 µg/kg lipopolysaccharide (LPS), SC), DEX group (200 µg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 µg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 µg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 µg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 µg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hr. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and caspase 3 and caspase 9 mRNA expression), biochemically (Superoxide dismutase activity (SOD), Glutathione (GSH), and malondialdehyde levels (MDA)) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Results: Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-α, VEGF, caspase 9, and caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Conclusion: Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.
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The florescence characteristics and the toxicities of carbon nanodots (CDs) are directly related to their elemental compositions. Fluorescent and non-toxic agent for imaging of biological systems was aimed. Sulfur and nitrogen co-doped CDs (S/N-CDs) was hydrothermally produced in an average size of 8 nm. S/N-CDs showed blue fluorescence under UV-light with an excitation wavelength of 365 nm. After 24 h, S/N-CDs was non-cytotoxic in HUVEC and L929 cells. S/N-CDs have a great potential to act as an alternative material for commercial fluorescent materials with its 85.5% of quantum yield. S/N-CDs was approved in vitro as an imaging agent for an ocular fundus angiography of rats.
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Carbono , Puntos Cuánticos , Animales , Ratas , Nitrógeno , Fondo de Ojo , Azufre , Colorantes Fluorescentes , AngiografíaRESUMEN
Inflammation involves a long chain of molecular reactions and cellular activity designed to repair tissue damaged by various causes. The inflammatory process and its complex mechanisms have recently become a focus of interest for many researchers. After the onset of inflammation, various adverse conditions that initiate the inflammatory response need to be addressed; however, failure to limit the inflammatory reaction may result in the damage or destruction of host cells. Therefore, inflammatory reactions play a role in many diferent diseases. Aquaporins (AQPs), commonly referred to as water channels, are protein channels responsible for forming pores in the membranes of biological cells. Their main function is to aid in the movement of water between cells. Aquaporins not only regulate transepithelial fluid transport across membranes but also play a role in regulating essential events crucial for the inflammatory response. Aquaporins have been shown in many studies to have important roles in inflammatory diseases. This clearly indicates that AQPs may be potential targets for inflammatory diseases. This review summarizes the research to date on the structure and function of AQPs and provides an update on the relationship between AQPs and various human inflammatory diseases.
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Urotensin-II (UT-II) is the most powerful vasoconstrictor agent and is known to play a role in heart failure, diabetes, pulmonary hypertension and asthma. The effect of passive smoking on UT-II levels is unknown. The present study aims to evaluate serum UT-II levels in children exposed to passive smoke. The study included a total of 120 children; 47 children not exposed to passive smoke were included in Group 1 (control group), and 73 children exposed to passive smoke were included in Group 2. Serum samples of the participants were stored at -80 °C after centrifugation and were assessed at least two times with high-precision human ELISA kits. Serum UT-II levels were significantly higher in the children exposed to passive smoke than in the children not exposed. Furthermore, Group 2 was grouped according to the number of cigarettes smoked at home per day, type of passive smoking (second-hand smoke or third-hand smoke), and how many people in their family and/or living together smoked. There was a positive correlation between the number of cigarettes they were exposed to per day and serum UT-II levels. Passive smoking in childhood may be associated with high serum UT-II levels.
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Asma , Contaminación por Humo de Tabaco , Urotensinas , Asma/sangre , Asma/etiología , Niño , Humanos , Urotensinas/sangreRESUMEN
The aim of this study was to investigate the effects of red dragon fruit (Hylocereus polyrhizus) extract (DFE) on the stomach in ulcer model induced by indomethacin in rats. Effects of DFE were evaluated in indomethacin-induced gastric damage model on Sprague-Dawley rats. Experimental model: all rats were fasted for 24 h. At the end of this period, DFE was administered to the ulcer-induced groups. One hour after this application, a dose of 25 mg/kg of indomethacin was applied by oral gavage to all groups except the HEALTHY and DFE1000 groups. Six hours after indomethacin administration, the rats were euthanized with high-dose anesthesia and the experiment was terminated. Macroscopic and microscopic analyses for investigating ulcerative area, molecular and biochemical analyses for oxidative damages investigation and molecular analyses for the effect mechanism of indomethacin and DFE were conducted on stomach tissues in the study. While oxidative stress-associated markers such as MDA, BAX, and Caspase 3 increased dramatically in the indomethacin group, GSH antioxidant levels decreased. It was observed that these parameters were significantly improved in DFE 500 mg/kg and DFE 1000 mg/kg groups compared to ulcer group, and the results of especially DFE 1000 mg/kg group were similar to famotidine group. We observed that our histopathological findings also supported all our other findings. Dragon fruit extract was protected against indomethacin-induced ulcer damage by decreased MDA levels, increased GSH levels, and inhibition of Caspase 3, BAX, and Cox-2, and activation of Cox-1. PRACTICAL APPLICATIONS: People of all ages around the world suffer from gastric ulcer which is one of the most common gastrointestinal ailments. The etiological factors of the disease are using of cigarette and alcohol, nutritional deficiencies, infections, and using non-steroidal anti-inflammatory drugs which use frequent and indiscriminate. Indomethacin is one of the NSAIDs and is commonly preferred to induce ulcer modeling in rats due to its gastric toxicity potential. Current anti-ulcer drugs have many serious side effects. Patients who suffered from gastric ulcer tend to discontinue the drug because of side effects. Therefore, patients need new agents that are non-toxic, have few side effects, and are easily accessible anti-ulcer drugs. Dragon fruit, as a medicinal herb, is highly valuable and widely used in traditional medicine, and may provide gastroprotective activity. Studies have shown that H. polyrhizus has antioxidant activities. We consider the effects of dragon fruit extract (DFE) to be a therapeutic drug for an indomethacin-induced ulcer model.
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Antiinflamatorios no Esteroideos , Antiulcerosos , Cactaceae , Extractos Vegetales , Úlcera Gástrica , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Antiulcerosos/farmacología , Antioxidantes/farmacología , Cactaceae/química , Caspasa 3 , Frutas , Mucosa Gástrica , Indometacina/efectos adversos , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Proteína X Asociada a bcl-2RESUMEN
AIM: We aimed to investigate the effects of rasagiline on acute lung injury that develops in the sepsis model induced with the cecal ligation and puncture in rats. MAIN METHODS: The rats were separated into the following six groups, Group 1: Sham, Group 2: Sham + Rasagiline 4 mg/kg, Group 3: Sepsis, Group 4: Sepsis + Rasagiline 1 mg/kg, Group 5: Sepsis + Rasagiline 2 mg/kg, Group 6: Sepsis + Rasagiline 4 mg/kg. A total of four holes were opened with a 16-gauge needle through the cecum distal to the point of ligation. KEY FINDINGS: Rasagiline treatment increased glutathione level and superoxide dismutase activity while decreased the malondialdehyde level after the sepsis. There was a statistically significant improvement in the doses of 2 mg/kg and 4 mg/kg. Rasagiline also increased Tnf-α, IL1ß, IL6, NF-κßand HMGB1 gene expressions in dose-dependent at 2 mg/kg and 4 mg/kg doses. In increased doses, rasagiline prevent the development of edema, the formation of inflammation, and hemorrhage. SIGNIFICANCE: Rasagiline exerts both antioxidant and anti-inflammatory effects on the cecal ligation and puncture induced acute lung injury in rats.
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Lesión Pulmonar Aguda , Sepsis , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Animales , Ciego/metabolismo , Ciego/patología , Modelos Animales de Enfermedad , Indanos , Ligadura , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Sepsis/tratamiento farmacológico , Sepsis/metabolismoRESUMEN
AIM: Ovarian ischemia-reperfusion (I/R) injury is a serious gynecological condition that affects women of reproductive age and reduces ovarian reserve. Management of I/R injury with detorsion causes reperfusion damage, in which oxidative stress plays a central role. This study aimed to investigate whether the gossypin (GOS) with antioxidant properties, a flavonoid, has beneficial effects on the biochemical, molecular, and histopathological aspects of ovarian I/R injury. METHODS: Thirty-three female Balb/c mice were randomly divided into five groups as follows: Healthy (Sham-operated control group), I/R (IR group), I/R + GOS 5 (I/R with GOS 5 mg/kg), I/R + GOS 10 (I/R with GOS 10 mg/kg), and I/R + GOS 20 (I/R with GOS 20 mg/kg). This was followed by 3 h of ischemia and subsequent reperfusion for 3 h after detorsion was exposed. GOS was injected 2 h before reperfusion. RESULTS: IL-1ß, IL-6, TNF-α, NF-κB, and CASP-3 mRNA expressions, SOD (superoxide dismutase) activity, GSH (glutathione), and MDA (malondialdehyde) levels, and histopathological changes were evaluated in ovarian tissue. Histological examination indicated that treatment of ovarian I/R injury with GOS led to the improvement of ovarian tissue, which was accompanied by an increase in SOD activity and GSH level and a decrease in MDA level, NF-κB, TNF-α, IL-1ß, and IL-6 expressions. GOS was also corrected by reducing the elevated expression of CASP-3 as apoptosis-change marker. CONCLUSION: These findings indicate that the treatment of GOS may be useful as a conservative approach to reverse I/R injury via amelioration of oxidative stress parameters and histopathological scores, attenuation of inflammation, and the suppression of apoptosis.
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Ovario , Daño por Reperfusión , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Femenino , Flavonoides/metabolismo , Flavonoides/farmacología , Isquemia , Malondialdehído/metabolismo , Ratones , Ovario/patología , Estrés Oxidativo , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & controlRESUMEN
One of the most common health problems today, diabetes is a serious, chronic, and complex disease characterized by high blood glucose levels. Nowadays, experimental diabetes models are being developed to study existing diabetes in depth, to improve diabetes medications, or to develop new medications. The protocols developed to date to create an experimental diabetes model are finalized in different time intervals and depending on various factors. With these models, which can be designed in vivo and in vitro, a picture similar to type 1 and type 2 diabetes can be created. In this review, we aimed to present the methodology, advantages, and disadvantages of all currently used experimental diabetes models in the light of current literature.
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The aim of the study was to examine the protective effects and possible mechanism of gossypin against isoproterenol (ISO)-mediated myocardial damage in vivo and H9c2 cell damage in vitro. H9c2 cells were categorized into five groups. Viability was evaluated with MTT and LDH release in H9c2 cells. Apoptotic parameter analysis was performed with cytochrome c (Cyt-c), caspase-3 (CASP-3), and BCL2/Bax mRNA expression levels. In vivo, gossypin was administered orally to mice at doses of 5, 10, and 20 mg/kg for 7 days. ISO groups were injected with isoproterenol (150 mg/kg) subcutaneously (on 8th and 9th) for 2 days. Afterward, lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) levels and Troponin-I (Tn-I) amount from their serum, oxidative stress parameters superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) levels, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1 ß), and NF-kB mRNA expression levels with inflammatory markers from heart tissue were evaluated. In addition, IL-1B, BCL-2, and cas-3 immunohistochemical staining was performed from heart tissue and TNF-a level was measured by ELISA method. Administration of Gossypin protected the cells by dose-dependent, eliminating the reduced cell viability and increased LDH release of ISO in H9c2 cells. In mice serum analyses, increased LDH, CK-MB levels, and Tn-I levels were normalized by gossypin. ISO administration in heart tissue is regulated by gossypin with increased SOD activity, GSH amount, TNF-α, IL-6, IL-1ß, and NF-kB mRNA expression levels and decreased MDA amount. Overall, the present results demonstrated that gossypin has a potential cardioprotective treatment for ischemic heart disease on in vivo and in vitro.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Flavonoides/farmacología , Infarto del Miocardio/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Cardiotoxicidad , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Isoproterenol , Masculino , Ratones Endogámicos BALB C , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , RatasRESUMEN
BACKGROUND: We investigated whether levosimendan prevents contrast medium nephrotoxicity with glycerol aggravation in rats. METHODS: Forty-eight Wistar albino rats were assigned to eight groups (n = 6 × 8). No medication was administered to group I (controls); glycerol (intramuscular injection of 25% glycerol, 10 mL/kg) group II; intravenous iohexol 10 mL/kg to group III; glycerol and iohexol to group IV; iohexol and intraperitoneal levosimendan 0.25 mg/kg to group V; glycerol, iohexol, and levosimendan 0.25 mg/kg to group VI; iohexol and levosimendan 0.5 mg/kg to group VII; and glycerol, iohexol, and levosimendan 0.5 mg/kg to group VIII. One-day water withdrawal and glycerol injection prompted renal damage; iohexol encouraged nephrotoxicity; levosimendan was administered 30 min after glycerol injection and continued on days 2, 3, and 4. The experiment was completed on day 5. Serum blood urea nitrogen (BUN) and creatinine levels, superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α), nuclear factor kappa ß (NFK-ß), interleukin 6 (IL-6), and histopathological marks were assessed. One-way analysis of variance and Duncan's multiple comparison tests were used. RESULTS: Levosimendan changed serum BUN (p = 0.012) and creatinine (p = 0.018), SOD (p = 0.026), GSH (p = 0.012), and MDA (p = 0.011). Levosimendan significantly downregulated TNF-α (p = 0.022), NFK-ß (p = 0.008), and IL-6 (p = 0.033). Histopathological marks of hyaline and haemorrhagic cast were improved in levosimendan-injected groups. CONCLUSION: Levosimendan showed nephroprotective properties due to its vasodilator, oxidative distress decreasing and inflammatory cytokine preventing belongings.
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Fármacos Cardiovasculares , Glicerol , Animales , Fármacos Cardiovasculares/farmacología , Glicerol/farmacología , Estrés Oxidativo , Ratas , Ratas Wistar , Simendán/farmacologíaRESUMEN
This study aimed to investigate the effects of blood glucose control and the kidneys' functions, depending on fasting, in the streptozotocin-induced diabetes model in rats via TNF-α, NLRP-3, TGF-ß1 and VCAM-1 mRNA expression in the present study. 32 Wistar albino rats were allocated randomly into four main groups; H (Healthy, n = 6), HF (Healthy fasting, n = 6), D (Diabetes, n = 10), DF (Diabetes and fasting, n = 10). Blood glucose and HbA1c levels significantly increased in the D group compared to the healthy ones (p < 0.05). However, the fasting period significantly improved blood glucose and HbA1c levels 14 days after STZ induced diabetes in rats compared to the D group. Similar findings we obtained for serum (BUN-creatinine) and urine samples (creatinine and urea levels). STZ induced high glucose levels significantly up-regulated TNF-α, NLRP-3, TGF-ß1 and VCAM-1 mRNA expression and fasting significantly decreased these parameters when compared to diabetic rats. Histopathological staining also demonstrated the protective effects of fasting on diabetic kidney tissue. In conclusion, intermittent fasting regulated blood glucose level as well as decreasing harmful effects of diabetes on kidney tissue. The fasting period significantly decreased the hyperglycemia-related inflammatory cytokine damage on kidneys and also reduced apoptosis in favor of living organisms.
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Ayuno/metabolismo , Hiperglucemia/genética , Inflamación/genética , Riñón/patología , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Factor de Crecimiento Transformador beta1/genética , Factor de Necrosis Tumoral alfa/genética , Molécula 1 de Adhesión Celular Vascular/genética , Animales , Apoptosis/genética , Glucemia/metabolismo , Nitrógeno de la Urea Sanguínea , Caspasa 9/metabolismo , Creatinina/sangre , Creatinina/orina , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/orina , Ayuno/sangre , Hemoglobina Glucada/análisis , Hiperglucemia/sangre , Hiperglucemia/patología , Hiperglucemia/orina , Inflamación/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , ARN Mensajero/metabolismo , Ratas Wistar , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Urea/orina , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Purpose: To detect the presence of urotensin-2 (U-II) in the aqueous humor and evaluate the relationship between aqueous humor level and systemic diseases and pupil size. Methods: The study included 88 patients who underwent cataract surgery. Those with a pupil diameter (PD) of up to 4 mm were considered to have small dilation, those with 4-7 mm of dilatation were considered to have moderate dilation, and those with a PD of more than 7 mm considered to have large dilation. Patients with HT (hypertension) were classified as group 1, those with DM (diabetes mellitus) as group 2, and those with HT+DM as group 3, and those without any systemic disease as group 4. The U-II levels in humor aqueous samples taken from anterior chamber were measured. Results: When compared with the control group, it was observed that the level of U-II in the aqueous humor of the HT, DM, and DM+HT groups was significantly higher (P < 0.05). At the same time, when we compared the DM+HT group with the other groups, the level of U-II in the aqueous humor was significantly higher compared to the group with DM (P < 0.05). The U-II levels of the aqueous humor were higher in the patients with small pupils compared to the remaining groups (P < 0.005). Conclusion: U-II may play a role in small pupil pathophysiology. In addition, it was determined that patients with HT and/or diabetes had higher U-II levels in the aqueous humor than healthy individuals.
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Humor Acuoso/química , Diabetes Mellitus/diagnóstico , Miosis/diagnóstico , Urotensinas/análisis , Anciano , Catarata , Estudios Transversales , Diabetes Mellitus/cirugía , Femenino , Humanos , Masculino , Miosis/cirugía , Estudios ProspectivosRESUMEN
OBJECTIVE: The aim of this study was to explore the role of endothelin 1 (ET-1) in human breast cancer proliferation and migration and antagonism of endothelin receptor A (ETAR) and endothelin receptor B (ETBR) by using the non-selective dual ETA/ETB receptor antagonist bosentan and determine its anti-proliferative, anti-metastatic, and apoptotic effects demonstrated by nuclear factor kappa B (NF-kB), vascular endothelial growth factor (VEGF), Caspase 3 and Caspase 9 expression on endothelin-induced proliferation of MCF-7 cell line in vitro. MATERIALS AND METHODS: A total of 8,000 cells were seeded into e-plates 24 hours after the cells were incubated with or without 10-4 M BOS (1 hour before ET-1 treatment); 10-7, 10-8, and 10-9 M ET-1 for 1-4 days. RESULTS: Whether ET-1 is present or not in the tumor area, bosentan exerts anti-proliferative effect on breast cancer. However, ET-1 and bosentan group showed important inhibitory effect on tumor migration compared to bosentan alone, which can be attributed to increased activity of ET-1 axis in the presence of ET-1. The imbalance among the NF-kB, caspases, and VEGF, which are predictive factors of carcinogenesis significantly improved after bosentan administration. CONCLUSION: Our study definitely demonstrated ET-1 and its critical role in cancer progression with apoptotic and anti-apoptotic pathways (NF-κB) and VEGF expression, and migration analyses were also performed. The second major finding was that bosentan inhibited ET-1-mediated effects on tumor proliferation and migration.
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Aprepitant is a selective SP/NK-1 receptor antagonist and used in postoperative and chemotherapeutics induced emesis and vomiting. The aim of our study is to show aprepitant may have beneficial effects on gastrointestinal complaints in cancer patients undergoing chemotherapeutics by indomethacin-induced gastric ulcer model. A total of 48 rats were fasted 24 h for ulcer experiment. Aprepitant doses of 5, 10, 20, and 40 mg/kg were evaluated for their antiulcer activity. Omeprazole (20 mg/kg) was used as a positive control group. Six hours after 25 mg/kg indomethacin administration, all stomachs were dissected out. After macroscopic analyses, tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), COX-1, and COX-2 mRNA levels and SOD activity, and GSH and MDA levels of stomachs were determined. Histopathological examinations were evaluated. Aprepitant administration exerted 48.14%, 49.62%, 65.92%, and 76.77% ulcer inhibition effects at 5, 10, 20, and 40 mg/kg, respectively. Aprepitant administration decreased oxidative stress and inflammatory parameters in stomach tissues dose dependently. Aprepitant administration increased stomach COX-2 mRNA levels at 20 and 40 mg/kg doses. Although aprepitant appears to be disadvantageous in terms of treating gastric ulcer due to COX enzyme inhibition according to the previous studies, aprepitant has been shown to have ulcer healing effect in our study. When aprepitant is given as an anti-nausea and vomiting drug to cancer patients undergoing chemotherapy, we can argue that it will not be necessary to add a new gastric protective agent as it also shows beneficial effects in gastrointestinal complaints.
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Antieméticos/uso terapéutico , Aprepitant/uso terapéutico , Mediadores de Inflamación/antagonistas & inhibidores , Náusea/tratamiento farmacológico , Úlcera Gástrica/tratamiento farmacológico , Vómitos/tratamiento farmacológico , Animales , Antieméticos/farmacología , Aprepitant/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Mediadores de Inflamación/metabolismo , Masculino , Ratas , Ratas Wistar , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologíaRESUMEN
AIM: This study aimed to demonstrate the role of serotonin 7 receptor (5-HT7) and the effects of 5-HT7 agonists and antagonists in an indomethacin-induced gastric ulcer. MATERIAL AND METHOD: Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT7 agonist) and SB269970 (5-HT7 antagonist) were administered at 10 mg/kg as a pre-treatment. One hour after the drug treatments, 25 mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized. RESULTS: We analyzed the iNOS, eNOS, and 5-HT7 receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT7 mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT7 mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT7 agonist on gastric tissue. CONCLUSION: The study suggested that activation of 5-HT7 receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.
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Amidas/farmacología , Indometacina/farmacología , Piperazinas/farmacología , Receptores de Serotonina/metabolismo , Agonistas de Receptores de Serotonina/fisiología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Animales , Famotidina/farmacología , Expresión Génica/efectos de los fármacos , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fenoles/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Antagonistas de la Serotonina/farmacología , Úlcera Gástrica/metabolismo , Sulfonamidas/farmacologíaRESUMEN
Nasal polyposis (NP) is an inflammatory disease of the paranasal sinuses and nasal cavity. The primary purpose of our study is to determine the expression of 5-HT7 receptors both in nasal polyps and in healthy tissue in the nasal cavity. The subsequent aim is to compare the expression of 5-HT7 receptors in patients with NP and in inferior turbinate tissue (control).The study included 60 participants (40 with NP and 20 controls) aged 35 to 62 years. Nasal polyp samples were collected from all patients and relative 5-HT7 receptor expression analyses were performed. RT-PCR analysis of nasal polyps and control tissue identified 5-HT7 receptor expression in the nasal cavities of controls. This expression was approximately 67 times higher in nasal polyp tissue than in healthy tissue. Our study identifies the expression of 5-HT7 receptors in the nasal cavity for the first time. It is also the first demonstration of increased 5-HT7 receptor expression in tissue from nasal polyps, which occur in the paranasal sinuses and nasal cavity.
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BN has important roles in several physiological events, including bone growth and immune system. New infection-free cranioplasty and has an osteogenic activities material that are compatible with tissue are being developed. We aimed in our study to examine whether different combinations of Boron-nitride/Hydroxyapatite are embedded into the scaffold in the treatment of calvarial defects. 200 adult female Sprague-Dawley rats divided into 10 equal groups. Osteotomy was made by trepan drill in 8 mm diameter. The scaffolds were placed in the rats and were left to recovery for 2 months. During the experiment, CT scans were taken from the calvarial areas of the rats in the 2nd, 4th and 8th weeks. Significant healing was observed in defect diameters in 2.5% BN+10% HA, 2.5% BN and 5% BN+10% HA, respectively. After 8 weeks, it was seen that the amounts of OPN, BMP-2, RunX2 and ALP mRNA expression significantly decreased in 2.5% BN+10% HA, 2.5% BN, 5% BN+10% HA and 5% BN groups. It was shown that bone recovery was at the best grade in the groups, which contained 2.5% BN and 2.5% BN+10% HA when compared to the other groups. BN is a very promising agent that will be used in reconstructive surgery for the treatment of calvarial bone defects.
Asunto(s)
Durapatita , Nanopartículas , Animales , Regeneración Ósea , Boro , Femenino , Osteogénesis , Hueso Parietal , Ratas , Ratas Sprague-Dawley , Andamios del TejidoRESUMEN
INTRODUCTION: That EGCG has strong antioxidant and anti-inflammatory activities as well as antibacterial activity against many streptococcus species suggests that it may be beneficial in the treatment of AOM. OBJECTIVE: Aim of the study is to reveal the molecular and biochemical effects of EGCG on LPS induced otitis media in rats. METHODS: Forty-two male albino Wistar rats were randomly divided into 7 groups. Inflammation was induced by administrating 50⯵L of 1â¯mg/ml lipopolysaccharide (LPS). EGCG used 50 and 100â¯mg/kg/day and combined penicillin G (PENG) 48â¯h after LPS injection. RESULTS: The combined EGCG 50 and PENG group and the group with EGCG 50 alone showed the best anti-inflammatory effect on LPS-induced AOM. TNF-α and IL-1ß gene expression significantly down regulated EGCG 50 and combined with PENG compared to the otitis media group. The combination of PenG and EGCG 50 led to the best histopathological improvement. Both the inflammation and the membrane thickness of this group were at almost the same level as the healthy group and tympanum was seen normal. CONCLUSION: The results of this study make it clear that EGCG plays an important role in antioxidant and anti-inflammatory activity during AOM.