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1.
Clin Exp Pharmacol Physiol ; 49(2): 291-301, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34597426

RESUMEN

This study evaluated the mechanistic sequel of aldehyde dehyrogenase (ALDH2) and Klotho protein in cyclophosphamide (CP)-induced cardiotoxicity in rats and the protective effect of astaxanthin (AST) against that sequel. A total of 40 male Wistar albino rats were divided into four groups of 10 animals each: Group 1 was injected intraperitoneally (i.p.) with normal saline for 10 successive days. Group 2 was injected with normal saline for 5 days before and after a single dose of CP (200 mg/kg, i.p.). Group 3 received AST (50 mg/kg/day, i.p.) for 10 days. Group 4 received CP as group 2 and AST as group 3. After the last dose of the treatment protocol, serum was separated to measure cardiotoxicity indices and the left ventricle was then dissected for mRNA and protein expression studies and histopathological examinations. Treatment with CP significantly increased serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and troponin, while significantly decreased soluble α Klotho protein and caused histopathological lesions in cardiac tissues. In cardiac tissues, CP significantly decreased gene expression of ALDH2, Klotho protein, mTOR, IGF, AKT, AMPK, BCL2, but significantly increased expression of BAX and caspase-8. Interestingly, administration of AST in combination with CP completely reversed all the biochemical, histopathological and gene expression changes induced by CP to the control values. The current study suggests that inhibition of ALDH2, Klotho protein, mTOR, and AMPK signals in cardiac tissues may contribute to CP-induced acute cardiomyopathy. AST supplementation attenuates CP-induced cardiotoxicity by modulating ALDH2 and Klotho protein expression in heart tissues, along with its downstream apoptosis effector markers.


Asunto(s)
Aldehído Deshidrogenasa , Cardiomiopatías , Aldehído Deshidrogenasa/farmacología , Animales , Cardiomiopatías/inducido químicamente , Cardiomiopatías/prevención & control , Ciclofosfamida/toxicidad , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Xantófilas
2.
Artículo en Inglés | MEDLINE | ID: mdl-33846129

RESUMEN

Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data are limited describing the use and safety of liposomal amphotericin B (L-AMB). Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AEs). Analysis was performed to evaluate for predictors of worse outcomes. Forty-two patients (67% male, median age 50 years) were identified, most of whom were treated for histoplasmosis. The most common doses of L-AMB were 3 mg/kg (n = 16, 38%) or 5 mg/kg (n = 14, 33%) based on actual body weight. Twenty-six (62%) patients completed their anticipated course of L-AMB. Twenty-two (52%) patients were readmitted within 30 days of discharge; median time to readmission was 11 days (interquartile range [IQR] 5 to 18). While hypokalemia and acute kidney injury (AKI) were common, occurring in 26 (62%) and 20 (48%) patients, respectively, only 5 (12%) were readmitted to the hospital due to L-AMB-associated AEs. Ninety percent of patients achieved at least partial renal recovery within 30 days after L-AMB discontinuation. Factors significantly associated with AKI include higher L-AMB dose, lower serum potassium levels after therapy initiation, and receipt of potassium supplementation at discharge. L-AMB is associated with significant AEs; however, these results suggest that treatment is feasible in the outpatient setting with close monitoring, as the majority of AEs were managed effectively in an outpatient without long-term sequelae.


Asunto(s)
Antiinfecciosos , Pacientes Ambulatorios , Anfotericina B , Antifúngicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
3.
Clin Exp Pharmacol Physiol ; 48(6): 911-920, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33783002

RESUMEN

Imatinib (IM) is a pharmaceutical drug that inhibits tyrosine kinase enzymes that are responsible for the activation of many proteins by signal transduction cascades as c-Abl, c-Kit and the platelet-derived growth factor (PDGF) receptor. Thymoquinone (TQ) is an active constituent of Nigella sativa seeds. Thymoquinone benefits are attributed to its medicinal uses as antioxidant, anticancer and antimicrobial agent. This study aimed to investigate the impact of using TQ with IM in the HCT116 human colorectal cancer cell line model. The HCT116 cells were treated with IM or/and TQ in non-constant ratios, in which the fixed concentrations of TQ (5, 10 or 20 µmol/L) were co-treated with various concentrations of IM (7.5-120 µmol/L) for 24, 48 and 72 hours. Imatinib-TQ interaction was analysed using CompuSyn software. The IC50 values for IM were 105, 72 µmol/L after 48 and 72 hours, respectively, and were significantly reduced to 7.3, 7 and 5.5 µmol/L after combination with TQ (10 µmol/L) and to 5.8, 5.6 and 4.6 µmol/L after combination with TQ (20 µmol/L) to 24, 48 and 72 hours, respectively. The combination index (CI) and dose reduction index (DRI) values indicate a significant synergism in HCT-116 cells at different treatment time points. Thymoquinone significantly enhances the cellular uptake of IM in HCT116 cells in a time and concentration-dependent manner. A significant downregulation in ATP-binding cassette (ABC) subfamily B member 1 (ABCB1), ABC subfamily G member 2 (ABCG2) and human organic cation transporter 1 (hOCT1) genes was observed in the cells exposed to IM+TQ combination as compared to IM alone, which resulted in a substantial elevation in uptake/efflux ratio in combination group. In conclusion, TQ potentiates IM efficacy on HCT116 cells via uptake/efflux genes modulation.


Asunto(s)
Mesilato de Imatinib , Subfamilia B de Transportador de Casetes de Unión a ATP , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Benzoquinonas , Línea Celular Tumoral , Humanos , Proteínas de Neoplasias , Transducción de Señal
4.
Andrologia ; 53(8): e14126, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34101882

RESUMEN

In this study, we estimated the protective role of Moringa oleifera leaf ethanolic extract (MOLE) against obesity-associated testicular dysfunction. Fifty male albino rats were randomly assigned to five groups (n = 10): Group I (basal diet), group II (basal diet plus MOLE orally), group III (high-fat diet-HFD), group IV (HFD plus oral MOLE) and group V (HFD for 8 weeks followed by a basal diet plus oral MOLE for 6 weeks). The study duration extended for 14 weeks. Serum collected to investigate testosterone, FSH and LH levels. Testicular tissues were used to determine levels of SOD, glutathione, catalase and malondialdehyde. Semen was collected to estimate its quality (morphology, motility and concentration). Morphological changes in the testis were investigated by histopathological and immunohistochemical techniques. Compared with both control treatment and MOLE treatment, serum testosterone, FSH, LH, testicular enzymatic catalase, SOD, GSH, survivin immunoreactivity, sperm quality and testicular weight were all significantly decreased in rats treated with HFD, while there were significant increases in testicular malondialdehyde and caspase-3 immunoreactivity. MOLE improved all harmful effects of HFD. Improvements were more pronounced in the protected (G 4) than the treated (G 5) group. MOLE could be a potential solution for obesity-associated fertility problem.


Asunto(s)
Moringa oleifera , Animales , Masculino , Malondialdehído , Obesidad/tratamiento farmacológico , Obesidad/etiología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Testículo
5.
Environ Toxicol ; 36(8): 1521-1535, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33885218

RESUMEN

This study evaluated the ameliorative impact of Nigella sativa oil (NSO) on emamectin benzoate (EMB) neurotoxicity. Thirty-five male rats were randomly allocated into 5 groups (n = 7). G1 (control): received distilled water; G2: received NSO (3 ml. Kg-1 B.W.) for 6 weeks; G3: received EMB (9 mg kg-1 B.W.) for 6 weeks; G4: was co-treated with NSO and EMB for 6 weeks; G5: was treated with EMB for 4 weeks then, received NSO for 2 weeks. All treatments were given orally every other day. EMB increased serum urea, creatinine levels; brain dopamine, serotonin, malondialdehyde levels; brain expression levels of caspase 3 and TNF-α. While, it decreased serum total protein, albumin, brain GABA, AChE, GSH-Px, CAT, and SOD levels. Histopathological findings revealed hemorrhage, congestion, severe degeneration, and edema of the brain tissues. NSO reversed the EMB-induced biochemical and histopathological alterations. This NSO effect is mostly due to its antioxidant, antiinflammatory, and antiapoptotic activities. These findings suggest NSO as a potential protective and therapeutic agent for EMB-induced neurotoxicity.


Asunto(s)
Antioxidantes , Aceites de Plantas , Animales , Ivermectina/análogos & derivados , Masculino , Malondialdehído , Ratas
6.
Andrologia ; 52(11): e13811, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32897594

RESUMEN

The current study aimed to investigate the protective potential of Chlorella Vulgaris (CV) extract against the reproductive dysfunction induced by sodium nitrite toxicity. Forty-five male Wistar albino rats were assigned into five groups (n = 9). Control group received normal saline orally for 3 months, CV-treated: administered CV extract (70 mg/kg.BW) orally for 3 months, sodium nitrite-treated: received sodium nitrite (80 mg/kg.BW) orally for 3 months, co-treated: simultaneously received CV along with sodium nitrite treatment, orally, daily for 3 months, and CV-pre-treated: pre-treated with CV extract for 4 weeks followed by simultaneous treatment with sodium nitrite and CV extract for additional 8 weeks. Treatment with sodium nitrite significantly decreased serum testosterone and follicle-stimulating hormone concentrations, sperm count, motility, and viability. Besides, it decreased testicular superoxide dismutase and glutathione peroxidase activities while increased malondialdehyde concentration. This effect of sodium nitrite was associated with degenerative, necrotic, vascular, and inflammatory changes in testicular tissues. Treatment of sodium nitrite-intoxicated rats with CV in co-treated and pre-treated groups significantly prevented sodium nitrite-induced alterations of sperm parameters, hormonal concentrations, testicular oxidative-antioxidant status, and histological architecture. This study indicates that CV extract ameliorates the reproductive dysfunction induced by sodium nitrite toxicity via improving reproductive hormonal levels and testicular antioxidant activities.


Asunto(s)
Chlorella vulgaris , Nitrito de Sodio , Testículo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Humanos , Masculino , Metanol , Estrés Oxidativo , Extractos Vegetales/toxicidad , Ratas , Ratas Wistar , Nitrito de Sodio/toxicidad , Recuento de Espermatozoides , Motilidad Espermática , Espermatozoides/metabolismo , Testículo/efectos de los fármacos , Testículo/metabolismo
7.
Toxicol Mech Methods ; 30(7): 526-535, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32456565

RESUMEN

Purpose: Cancer rates have been increased among women of reproductive age nowadays. Hence, many young female will be exposed to chemotherapeutic agents as cyclophosphamide (CP), carrying the hazards on female fertility. Cilostazol is a selective phosphodiesterase-3 inhibitor drug which exhibits antioxidant, anti-inflammatory, and anti-apoptotic activities. We aimed in this study to explore the possible protective effects of cilostazol against CP-induced ovarian damage in female rats.Methods: Cilostazol (10 mg/kg/day) was administered orally for 10 days in presence and absence of CP (150 mg/kg IP single dose) treatment. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and anti-Müllerian hormone (AMH) levels were determined. Ovarian oxidative stress parameters along with inflammatory biomarkers were measured. 3,5-Cyclic adenosine monophosphate (cAMP) ovarian level was detected. Ovarian histopathological examination and caspase-3 immunohistochemical study were evaluated.Results: CP-treated rats showed a significant increase in serum levels of FSH and LH with decreased serum E2 and AMH levels with an increase in the ovarian inflammatory and oxidative stress biomarkers besides a significant decrease in cAMP ovarian level with an evident histopathological picture of ovarian damage and a high caspase-3 immunoexpression. Cilostazol pretreatment significantly restored the distributed hormonal levels, the oxidative stress and inflammatory biomarkers to their normal levels with marked improvement in histopathological picture of ovarian damage with a significant decrease in caspase-3 immunoexpression.Conclusions: These data suggest that cilostazol protects against CP- induced ovarian damage, which may be related to an increase in cAMP with subsequent anti-inflammatory, antioxidant, and anti-apoptotic properties.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Alquilantes/toxicidad , Antioxidantes/farmacología , Cilostazol/farmacología , AMP Cíclico/metabolismo , Ciclofosfamida/toxicidad , Hemo Oxigenasa (Desciclizante)/metabolismo , Enfermedades del Ovario/prevención & control , Ovario/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Femenino , Hormonas/sangre , Mediadores de Inflamación/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedades del Ovario/inducido químicamente , Enfermedades del Ovario/enzimología , Enfermedades del Ovario/patología , Ovario/enzimología , Ovario/patología , Estrés Oxidativo/efectos de los fármacos , Ratas
8.
Andrologia ; 50(5): e12996, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29527696

RESUMEN

This study aimed to investigate the protective potential of Royal jelly (RJ) against cadmium (Cd)-induced testicular dysfunction in rats. Thirty-five adult male Wistar rats were assigned into five groups. G I; (control) injected intraperitoneally with saline, G II injected intraperitoneally with a single dose of CdCl2 (1 mg/kg BW), G III received RJ (100 mg/kg BW/day) orally, G IV was pre-treated with RJ for 1 week then, treated with CdCl2 , and G V was co-treated with RJ and CdCl2 . After day 56, serum and tissue samples were collected and analysed. The results showed decreased serum testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), superoxide dismutase, glutathione reductase, sperm motility and count while increased malondialdehyde, nitric oxide, tumour necrosis factor-α (TNF-α) and sperm abnormalities, along with a severely damaged seminiferous tubules epithelium with cytoplasmic and nuclear disruptions following Cd toxicity. Additionally, Cd stimulated testicular mRNA expression of TNF-α while inhibited those of steroidogenic acute regulatory protein, cytochrome P450 cholesterol side chain cleavage enzyme androgen binding protein, FSH-receptor, LH-receptor, androgen receptor, 3ß-hydroxysteroid dehydrogenase (HSD), 17ß-HSD, and cytochrome P450 17A1. These negative alterations of cadmium were greatly reduced by RJ treatment. This study concluded that RJ protects against Cd-induced testicular toxicity.


Asunto(s)
Antioxidantes/uso terapéutico , Cadmio/efectos adversos , Ácidos Grasos/uso terapéutico , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Animales , Hormona Folículo Estimulante/sangre , Glutatión Reductasa/sangre , Hormona Luteinizante/sangre , Masculino , Malondialdehído/sangre , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Superóxido Dismutasa/sangre , Testosterona/sangre
9.
Transgenic Res ; 26(2): 197-207, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27900537

RESUMEN

Rice black-streaked dwarf virus (RBSDV), a member of the genus Fijivirus in the family Reoviridae, causes significant economic losses in rice production in China and many other Asian countries. Development of resistant varieties by using conventional breeding methods is limited, as germplasm with high level of resistance to RBSDV have not yet been found. One of the most promising methods to confer resistance against RBSDV is the use of RNA interference (RNAi) technology. RBSDV non-structural protein P7-2, encoded by S7-2 gene, is a potential F-box protein and involved in the plant-virus interaction through the ubiquitination pathway. P8, encoded by S8 gene, is the minor core protein that possesses potent active transcriptional repression activity. In this study, we transformed rice calli using a mini-twin T-DNA vector harboring RNAi constructs of the RBSDV genes S7-2 or S8, and obtained plants harboring the target gene constructs and the selectable marker gene, hygromycin phosphotransferase (HPT). From the offspring of these transgenic plants, we obtained selectable marker (HPT gene)-free plants. Homozygous T5 transgenic lines which harbored either S7-2-RNAi or S8-RNAi exhibited high level resistance against RBSDV under field infection pressure from indigenous viruliferous small brown planthoppers. Thus, our results showed that RNA interference with the expression of S7-2 or S8 genes seemed an effective way to induce high level resistance in rice against RBSD disease.


Asunto(s)
Resistencia a la Enfermedad/genética , Proteínas F-Box/genética , Oryza/genética , Enfermedades de las Plantas/genética , China , Oryza/crecimiento & desarrollo , Oryza/virología , Enfermedades de las Plantas/virología , Virus de Plantas/genética , Virus de Plantas/patogenicidad , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/virología , Interferencia de ARN , Reoviridae/genética , Reoviridae/patogenicidad
10.
BMC Complement Altern Med ; 17(1): 45, 2017 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-28086769

RESUMEN

BACKGROUND: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-ß), type I TGF-ß receptor (TßR-1), type II TGF-ß receptor (TßR-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR. RESULTS: Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl4 group. The CCl4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-ß, TßR-I, TßR-II, MMP2, MMP9, Smad-2,-3, -4, and IL-8 compared with the control group. However, CCl4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: ginseng extract had an anti-fibrosis effect via the regulation of the TGF-ß1/Smad signaling pathway in the CCl4-induced liver fibrosis model. The major target was the inhibition of the expression of TGF-ß1, Smad2, and Smad3.


Asunto(s)
Cirrosis Hepática/tratamiento farmacológico , Panax/química , Extractos Vegetales/administración & dosificación , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Tetracloruro de Carbono/efectos adversos , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Masculino , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Wistar , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Smad/genética , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/genética
11.
Immunol Invest ; 45(4): 349-69, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27104958

RESUMEN

Dexamethasone (DEX) is a synthetic glucocorticoid with potent anti-inflammatory effects that is widely used to treat inflammatory diseases. The aim of the present study was to investigate the possible protective effect of DEX on the lipopolysaccharides (LPS)-induced acute lung injury (ALI) in a mouse model. Animals were pretreated with DEX (5 and 10 mg/kg, i.p.) for seven days and acute lung injury was induced by intranasal (i.n.) administration of LPS on day 7. In the present study, administration of LPS resulted in significant increase in neutrophils and lymphocytes count whereas a substantial reduction in T cell subsets (CD3(+) and CD4(+)) and pro-inflammatory (IL-6 and TNF-α) cytokines occurred, which were reversed by DEX treatment. RT-PCR analysis revealed an increased mRNA expression of IL-6, TNF-α, COX-2, iNOS, and NF-κB p65 and decreased IL-10 in the LPS group, which were reversed by treatment with DEX in lung tissues. Western blot analysis revealed an increased expression of COX-2, iNOS and NF-κB p65 in the LPS-group, which was reduced by treatment with DEX. Compared with the LPS group, the DEX treatment also demonstrated a considerable increase in the protein expression level of IL-10 cytokine. Administration of LPS resulted in marked increase in malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity whereas noticeable decrease in glutathione (GSH) content. These changes were significantly reversed by treatment with DEX. The histological examinations revealed protective effect of DEX while LPS group aggravated lung injury. The present findings demonstrate the potent anti-inflammatory action of the DEX against acute lung injury induced by LPS.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Dexametasona/uso terapéutico , Interleucina-10/metabolismo , Pulmón/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Animales , Células Cultivadas , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-10/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/inmunología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/genética , FN-kappa B/metabolismo , Neutrófilos/inmunología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
12.
Immunology ; 145(3): 391-403, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25684443

RESUMEN

Airway epithelial cells (AECs) express a variety of receptors, which sense danger signals from various aeroallergens/pathogens being inhaled constantly. Proteinase-activated receptor 2 (PAR-2) is one such receptor and is activated by cockroach allergens, which have intrinsic serine proteinase activity. Recently, dual oxidases (DUOX), especially DUOX-2, have been shown to be involved in airway inflammation in response to Toll-like receptor activation. However, the association between PAR-2 and DUOX-2 has not been explored in airways of allergic mice. Therefore, this study investigated the contribution of DUOX-2/reactive oxygen species (ROS) signalling in airway reactivity and inflammation after PAR-2 activation. Mice were sensitized intraperitoneally with intact cockroach allergen extract (CE) in the presence of aluminium hydroxide followed by intranasal challenge with CE. Mice were then assessed for airway reactivity, inflammation, oxidative stress (DUOX-2, ROS, inducible nitric oxide synthase, nitrite, nitrotyrosine and protein carbonyls) and apoptosis (Bax, Bcl-2, caspase-3). Challenge with CE led to up-regulation of DUOX-2 and ROS in AECs with concomitant increases in airway reactivity/inflammation and parameters of oxidative stress, and apoptosis. All of these changes were significantly inhibited by intranasal administration of ENMD-1068, a small molecule antagonist of PAR-2 in allergic mice. Administration of diphenyliodonium to allergic mice also led to improvement of allergic airway responses via inhibition of the DUOX-2/ROS pathway; however, these effects were less pronounced than PAR-2 antagonism. The current study suggests that PAR-2 activation leads to up-regulation of the DUOX-2/ROS pathway in AECs, which is involved in regulation of airway reactivity and inflammation via oxidative stress and apoptosis.


Asunto(s)
Asma/inmunología , Inflamación/inmunología , NADPH Oxidasas/inmunología , Receptor PAR-2/inmunología , Hipersensibilidad Respiratoria/inmunología , Alérgenos/inmunología , Animales , Antiinfecciosos/inmunología , Antiinfecciosos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Asma/metabolismo , Asma/prevención & control , Compuestos de Bifenilo/inmunología , Compuestos de Bifenilo/farmacología , Western Blotting , Cucarachas , Modelos Animales de Enfermedad , Oxidasas Duales , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Inflamación/metabolismo , Inflamación/prevención & control , Masculino , Ratones Endogámicos BALB C , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Compuestos Onio/inmunología , Compuestos Onio/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Piperazinas/inmunología , Piperazinas/farmacología , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Receptor PAR-2/antagonistas & inhibidores , Receptor PAR-2/metabolismo , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/prevención & control , Sistema Respiratorio/inmunología , Sistema Respiratorio/metabolismo , Sistema Respiratorio/patología , Transducción de Señal/inmunología , Regulación hacia Arriba/inmunología
13.
Biosci Biotechnol Biochem ; 79(4): 598-609, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25420097

RESUMEN

The present study investigated the anti-obesity effects of pomegranate (Punica granatum) juices from the two Saudi Arabian, Taif red, Taif white, and Egyptian pomegranates in high-fat diet (HFD)-induced obese rats. Administrating any of the used juices decreased the body weight gain, food consumption, and serum levels of lipid, leptin, and glucose, while it increased serum insulin level. Histologically, all types of juices decreased the number and size of lipid droplets in hepatocytes compared to the obese, non-treated animals. All juices types upregulated the hepatic mRNA expression of hormone-sensitive lipase, pyruvate kinase, and adiponectin in obese rats; the genes were all suppressed by HFD feeding. Additionally, the expression of fatty acid synthase, sterol regulatory element-binding protein-1c, and acetyl-CoA carboxylase1 was also upregulated by all types of juices. Conversely, ghrelin mRNA expression was downregulated by all used juices' types. These findings demonstrate that all types of tested juices protect against the HFD-induced obesity in rats.


Asunto(s)
Bebidas , Ingestión de Alimentos/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Lythraceae/química , Obesidad/dietoterapia , Aumento de Peso/efectos de los fármacos , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Animales , Glucemia/metabolismo , Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/efectos adversos , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Ghrelina/genética , Ghrelina/metabolismo , Insulina/sangre , Leptina/genética , Leptina/metabolismo , Gotas Lipídicas/química , Gotas Lipídicas/metabolismo , Masculino , Obesidad/etiología , Obesidad/genética , Obesidad/metabolismo , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismo , Ratas , Ratas Wistar , Esterol Esterasa/genética , Esterol Esterasa/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Triglicéridos/sangre
14.
Biol Res ; 48: 30, 2015 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-26062544

RESUMEN

BACKGROUND: Carbon tetrachloride (CCl4) induces hepatotoxicity in animal models, including the increased blood flow and cytokine accumulation that are characteristic of tissue inflammation. The present study investigates the hepato-protective effect of rutin on CCl4-induced hepatotoxicity in rats. RESULTS: Forty male Wistar rats were divided into four groups. Group I (control group) received 1 mL/kg of dimethyl sulfoxide intragastrically and 3 mL/kg olive oil intraperitoneally twice a week for 4 weeks. Group II received 70 mg/kg rutin intragastrically. Groups III and IV received CCl4 (3 mL/kg, 30 % in olive oil) intraperitoneally twice a week for 4 weeks. Group IV received 70 mg/kg rutin intragastrically after 48 h of CCl4 treatment. Liver enzyme levels were determined in all studied groups. Expression of the following genes were monitored with real-time PCR: interleukin-6 (IL-6), dual-specificity protein kinase 5 (MEK5), Fas-associated death domain protein (FADD), epidermal growth factor (EGF), signal transducer and activator of transcription 3 (STAT3), Janus kinase (JAK), B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra-large (Bcl-XL). The CCl4 groups showed significant increases in biochemical markers of hepatotoxicity and up-regulation of expression levels of IL-6, Bcl-XL, MEK5, FADD, EGF, STAT3 and JAK compared with the control group. However, CCl4 administration resulted in significant down-regulation of Bcl2 expression compared with the control group. Interestingly, rutin supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: CCl4 administration causes alteration in expression of IL-6/STAT3 pathway genes, resulting in hepatotoxicity. Rutin protects against CCl4-induced hepatotoxicity by reversing these expression changes.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Interleucina-6/metabolismo , Rutina/farmacología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Biomarcadores , Tetracloruro de Carbono , Factor de Crecimiento Epidérmico/metabolismo , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Expresión Génica/efectos de los fármacos , Quinasas Janus/metabolismo , Hígado/efectos de los fármacos , MAP Quinasa Quinasa 5/metabolismo , Masculino , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína bcl-X/metabolismo
15.
BMC Neurosci ; 15: 37, 2014 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-24593767

RESUMEN

BACKGROUND: Extraneuronal levels of the neurotransmitter glutamate in brain rise during aging. This is thought to lead to synaptic dysfunction and neuronal injury or death. To study the effects of glutamate hyperactivity in brain, we created transgenic (Tg) mice in which the gene for glutamate dehydrogenase (Glud1) is over-expressed in neurons and in which such overexpression leads to excess synaptic release of glutamate. In this study, we analyzed whole genome expression in the hippocampus, a region important for learning and memory, of 10 day to 20 month old Glud1 and wild type (wt) mice. RESULTS: During development, maturation and aging, both Tg and wt exhibited decreases in the expression of genes related to neurogenesis, neuronal migration, growth, and process elongation, and increases in genes related to neuro-inflammation, voltage-gated channel activity, and regulation of synaptic transmission. Categories of genes that were differentially expressed in Tg vs. wt during development were: synaptic function, cytoskeleton, protein ubiquitination, and mitochondria; and, those differentially expressed during aging were: synaptic function, vesicle transport, calcium signaling, protein kinase activity, cytoskeleton, neuron projection, mitochondria, and protein ubiquitination. Overall, the effects of Glud1 overexpression on the hippocampus transcriptome were greater in the mature and aged than the young. CONCLUSIONS: Glutamate hyperactivity caused gene expression changes in the hippocampus at all ages. Some of these changes may result in premature brain aging. The identification of these genomic expression differences is important in understanding the effects of glutamate dysregulation on neuronal function during aging or in neurodegenerative diseases.


Asunto(s)
Envejecimiento/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Glutamato Deshidrogenasa/metabolismo , Ácido Glutámico/metabolismo , Hipocampo/fisiología , Proteínas del Tejido Nervioso/metabolismo , Proteoma/metabolismo , Animales , Glutamato Deshidrogenasa/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Distribución Tisular , Transcriptoma , Regulación hacia Arriba
16.
Materials (Basel) ; 17(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38612098

RESUMEN

The flow behaviour of AA2060 Al alloy under warm/hot deformation conditions is complicated because of its dependency on strain rates (ε˙), strain (ε), and deformation modes. Thus, it is crucial to reveal and predict the flow behaviours of this alloy at a wide range of temperatures (T) and ε˙ using different constitutive models. Firstly, the isothermal tensile tests were carried out via a Gleeble-3800 thermomechanical simulator at a T range of 100, 200, 300, 400, and 500 °C and ε˙ range of 0.01, 0.1, 1, and 10 s-1 to reveal the warm/hot flow behaviours of AA2060 alloy sheet. Consequently, three phenomenological-based constitutive models (L-MJC, S1-MJC, S2-MJC) and a modified Zerilli-Armstrong (MZA) model representing physically based constitutive models were developed to precisely predict the flow behaviour of AA2060 alloy sheet under a wide range of T and ε˙. The predictability of the developed constitutive models was assessed and compared using various statistical parameters, including the correlation coefficient (R), average absolute relative error (AARE), and root mean square error (RMSE). By comparing the results determined from these models and those obtained from experimentations, and confirmed by R, AARE, and RMSE values, it is concluded that the predicted stresses determined from the S2-MJC model align closely with the experimental stresses, demonstrating a remarkable fit compared to the S1-MJC, L-MJC, and MZA models. This is because of the linking impact between softening, the strain rate, and strain hardening in the S2-MJC model. It is widely known that the dislocation process is affected by softening and strain rates. This is attributed to the interactions that occurred between ε and ε˙ from one side and between ε, ε˙, and T from the other side using an extensive set of constants correlating the constitutive components of dynamic recovery and softening mechanisms.

17.
Int J Gen Med ; 17: 1897-1908, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736667

RESUMEN

Purpose: This study was conducted to release the debate and examine the short-term impact of KT on the quadriceps muscle following arthroscopic surgery for partial meniscectomy. Patients and Methods: As part of a double-blind, randomized controlled trial, 40 people who had an arthroscopic partial meniscectomy (APM) were randomly put into two groups, A and B. Group A received Kinesio tape (KT) for the superficial heads of the quadriceps muscle, while group B received placebo KTk. After 10 minutes of KT application, the peak torque of both groups was measured using a Biodex isokinetic dynamometer. Results: Peak torque showed a significant increase in group A in comparison with group B during angular velocity 60◦/Sec. (F (1, 130) = 58.9, p <0.001, ƞ2 =0.31) and during angular velocity 180◦/Sec. (F (1, 38) = 25.0, p <0.001, ƞ2 =0.40). Conclusion: After APM, individuals experienced an immediate and significant improvement in the quadriceps' peak torque following KT application to the Rectus femoris, Vastus medialis, and Vastus lateralis muscles from origin to insertion.

18.
Saudi Dent J ; 36(6): 947-953, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38883903

RESUMEN

This in vitro study aimed to evaluate the additive manufacturing (AM) of cobalt chromium Co-Cr and titanium Ti alloy clasps for clinical use. After scanning the Ni-Cr die of the first molar, Akers' clasps were designed using computer-aided design/ computer-aided manufacturing (CAD/CAM). The clasps were manufactured from Co-Cr-W dental alloy and Ti-6Al-4V alloy powder using AM machines. Then, they were divided into two groups. The initial retentive force of the clasps was measured using a universal testing machine. Cyclic loading of the clasps was carried out by a specially designed insertion-removal testing apparatus in wet condition up to 5000 cycles. Retentive force was measured at 1000, 2000, 3000, 4000, and 5000 cycles. Moreover, the intaglio surface of each clasp was scanned using the scanner; and superimposition between the pre- and post-cycling clasp files was performed to evaluate deformation after cyclic loading. The fitting surfaces of retentive clasp tips were examined with a scanning electron microscope (SEM). Finally, it has been found that the initial retentive force for the Co-Cr group was 10.81 ± 0.37 N, and for the Ti group was 5.41 ± 0.18 N. Additionally, during the testing periods, both Co-Cr and Ti clasps continued to lose retentive force within the cycles of placement and removal. This effect was more prominent in the Co-Cr than in the Ti clasps. The distances between pre- and post-cycling in the retentive arm were -0.290 ± 0.11 mm and -0.004 ± 0.01 mm in Co-Cr and Ti alloys, respectively, and in the reciprocal arm were -0.072 ± 0.04 mm and -0.032 ± 0.04 mm in Co-Cr and Ti alloys, respectively. The retentive force required to remove the Ti clasps was found to be significantly lower than those required to dislodge the Co-Cr clasps. Co-Cr and Ti clasps lost significant amounts of retentive force from the initial use to the 3.5-year periods of simulated clinical use.

19.
Heliyon ; 10(4): e26400, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38390184

RESUMEN

The hexagonal close-packed (HCP) crystal structure of Mg alloys lead to poor formability as well as other undesirable mechanical behaviors in an otherwise highly sought-after alloy for commercial use. This study investigates the evolution of microstructure, texture, corrosion and mechanical behaviors in Mg-Zn-Mn (ZM31) alloy after processing using Equal Channel Angular Pressing (ECAP). Dynamic recrystallization was evident in the ECAP-processed samples, correlated with a substantial fiber structure, and resulted in the attainment of notable grain refinement and high lattice strain. Average grain sizes of 2.2 and 2 µm were achieved via 2 and 4-Pass Bc processing, respectively. This significant refinement yielded lower corrosion rates through enhancement of the thickness, coherency, and stability of formed protective oxide layers. The corrosion rate in the NaCl medium was substantially enhanced by 99.5% after four passes via route Bc. The recrystallized fine structure was found to have contributed to yield strength, ultimate strength, and microhardness improvements. Deformation enhanced yield and ultimate strengths by 132% and 64%, respectively. The distinctive grain refinement mechanism exhibited through the current ECAP procedure has potential to pave the way for novel and impactful utilizations of ZM31 in industries that demand exceptional mechanical and corrosion performance.

20.
J Clin Med ; 13(7)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38610732

RESUMEN

(1) Background: Neck pain intensity, psychosocial factors, and physical function have been identified as potential predictors of neck disability. Machine learning algorithms have shown promise in classifying patients based on their neck disability status. So, the current study was conducted to identify predictors of neck disability in patients with neck pain based on clinical findings using machine learning algorithms. (2) Methods: Ninety participants with chronic neck pain took part in the study. Demographic characteristics in addition to neck pain intensity, the neck disability index, cervical spine contour, and surface electromyographic characteristics of the axioscapular muscles were measured. Participants were categorised into high disability and low disability groups based on the median value (22.2) of their neck disability index scores. Several regression and classification machine learning models were trained and assessed using a 10-fold cross-validation method; also, MANCOVA was used to compare between the two groups. (3) Results: The multilayer perceptron (MLP) revealed the highest adjusted R2 of 0.768, while linear discriminate analysis showed the highest receiver characteristic operator (ROC) area under the curve of 0.91. Pain intensity was the most important feature in both models with the highest effect size of 0.568 with p < 0.001. (4) Conclusions: The study findings provide valuable insights into pain as the most important predictor of neck disability in patients with cervical pain. Tailoring interventions based on pain can improve patient outcomes and potentially prevent or reduce neck disability.

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