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Organic photovoltaic (OPV) cells have experienced significant development in the last decades after the introduction of nonfullerene acceptor molecules with top power conversion efficiencies reported over 19% and considerable versatility, for example, with application in transparent/semitransparent and flexible photovoltaics. Yet, the optimization of the operational stability continues to be a challenge. This study presents a comprehensive investigation of the use of a conjugated polyelectrolyte polymer (CPE-Na) as a hole layer (HTL) to improve the performance and longevity of OPV cells. Two different fabrication approaches were adopted: integrating CPE-Na with PEDOT:PSS to create a composite HTL and using CPE-Na as a stand-alone bilayer deposited beneath PEDOT:PSS on the ITO substrate. These configurations were compared against a reference device employing PEDOT:PSS alone, as the HTL increased efficiency and fill factor. The instruments with CPE-Na also demonstrated increased stability in the dark and under simulated operational conditions. Device-based PEDOT:PSS as an HTL reached T80 after 2500 h while involving CPE-Na in the device kept at T90 in the same period, evidenced by a reduced degradation rate. Furthermore, the impedance spectroscopy and photoinduced transient methods suggest optimized charge transfer and reduced charge carrier recombination. These findings collectively highlight the potential of CPE-Na as a HTL optimizer material for nonfluorine OPV cells.
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OBJECTIVE: The most prevalent brain-specific microRNA, MicroRNA-124, exhibits anti-inflammatory properties. Luteolin nano-formulation with Zn oxide in the form of L/ZnO NPs may boost anti-diabetic properties; however, its beneficial effect on miRNAs is yet unknown in diabetes. The effectiveness of L/ZnONPs supplements in preventing diabetic neurodegeneration by modulating inflammatory responses in a diabetic model was investigated. METHODS: A diabetic rat model was induced by a high-fat diet and streptozotocin (30 mg/kg I.P.). Plasma glucose, insulin, and HOMR-IR levels, as well as cytokines, lipid peroxidation, GSH/GSSG, and glucose transporter 1, were determined along with the tight junction proteins occludin (OCLN) and zona occludens 1 (ZO-1). Moreover, the expressions of brain CCAAT/enhancer-binding protein (C/EBPA mRNA), miR-124, glial fibrillary acidic protein (GFAP), and NF-kBp65 were measured alongside the histological investigation. RESULTS: The results revealed that L/ZnO NPs were able to diminish lipid peroxidation, increase the activity of antioxidant enzymes, and reduce inflammation under oxidative stress. Consequently, it was able to reduce hyperglycemia, elevate insulin levels, and improve insulin resistance. Besides, L/ZnO NPs upregulate miR-124, reduce C/EBPA mRNA, increase BCl-2, and inhibit apoptosis. The results indicate that diabetes raises BBB permeability via tight junction protein decline, which is restored following L/ZnO NPs treatment. Luteolin/ZnO NPs regulate miR-124 and microglia polarization by targeting C/EBPA and are expected to alleviate inflammatory injury via modulation of the redox-sensitive signal transduction pathways. Luteolin/ZnO NPs have a novel target for the protection of the BBB and the prevention of neurological complications in diabetes.
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Diabetes Mellitus Experimental , Insulinas , MicroARNs , Enfermedades Neuroinflamatorias , Óxido de Zinc , Animales , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Insulinas/farmacología , Luteolina/farmacología , MicroARNs/genética , Nanopartículas , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Estrés Oxidativo , ARN Mensajero , Proteínas de Uniones Estrechas , Óxido de Zinc/farmacologíaRESUMEN
The xenoestrogen bisphenol A (BPA), a commonly used industrial chemical, has been linked to endocrine disruption. The point of the study was to consider the effects of chronic BPA exposure on the respiratory system of adult female rats, and the potential mitigating benefits of Sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H2S) administration. Detect biomarkers in Bronchoalveolar lavage fluid (BALF), including total protein content, Total cell counts, Neutrophils %, ICAM (intercellular adhesion molecule)-1 and TGF-ß (Transforming growth factor beta). NaHS significantly reduced pro-inflammatory cytokines (IFN-ß and MCAF,) also reduce (i.e. VCAM-1, VEGF, VIM, MMP-2, MMP-9), and reduced malondialdehyde and augmented activities of SOD and GSH-PX. Notably, H2S induced a marked decrease in the expression levels of p-extracellular signal-regulated protein kinase (p-ERK), p-c-Jun N-terminal kinase (p-JNK), and p-p38, H2S inhibits BPA-induced inflammation and injury in alveolar epithelial cells. These results suggest NaHS may prevent inflammation via the suppression of the ERK/JNK/ p-p38MAPK signaling pathway, Subsequent inhibition of inflammation, epithelial cell injury, and apoptosis may be providing insight into potential avenues for the treatment of lung injury.
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Sulfuro de Hidrógeno , Lesión Pulmonar , Femenino , Ratas , Animales , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/prevención & control , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Estrés OxidativoRESUMEN
BACKGROUND: The natural compound's alternative and complementary uses have increased hopes for hepatocellular cancer treatment (HCC). OBJECTS: The goal of this study was to see if Piceatannol (PIC) in combination with cisplatin has a synergistic effect on N, N-nitrosodiethylamine (DEN)-induced HCC in rats. METHODS: Tissue antioxidant enzymes, malondialdehyde (MDA), and nuclear factor erythroid 2 related factors 2 (Nrf2) and tumor necrosis factor α (TNF-α) gene expression were all measured. Nuclear Factor Kabba B (NF-κB) was also tested, as well as hepatic caspase 3 and NAD (P) H quinone oxidoreductase 1 (NQO1). Liver specimens were subjected to histopathological analysis. RESULTS: When compared to the HCC group, piceatannol and/or cisplatin caused a significant improvement in liver function tests, as well as a significant modulation in Nrf2 gene expression and antioxidant enzyme activities, as well as a significant decrease in tissue MDA, TNF-α, NF-κB levels, NQO1 activity, and prompt and caspase-3 activities. When the PIC and/or cisplatin combination was compared to each of these compounds alone, the results were substantial. CONCLUSION: PIC in combination with cisplatin has been shown to have a synergistic anticancer impact through modulating Nrf2 and redox state. In addition, adding PIC to an HCC therapy plan that includes chemotherapeutic medicines may boost the efficacy of cisplatin while reducing its negative effects.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratas , Animales , Dietilnitrosamina/toxicidad , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/tratamiento farmacológico , Cisplatino , Factor 2 Relacionado con NF-E2 , Antioxidantes , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , FN-kappa B , Factor de Necrosis Tumoral alfa , Oxidación-ReducciónRESUMEN
Blastocystis hominis is a worldwide common enteric parasite. Its pathogenic potential has not yet been established, although many reports suggest that it may cause the development of various gastrointestinal symptoms. The aim of the present study is to evaluate the destructive effect of different doses of cytotoxic gamma (γ) irradiation combined with and compared to metronidazole (MTZ) on Blastocystis spp. in vitro. The detection of the parasite in the stool specimen was conventionally done by light microscopic examination of direct smears, cultivation, followed by PCR-sequencing. Evaluation of γ-irradiation and MTZ effects on B. hominis was carried out by trypan blue exclusion assay, caspase activity detection, acridine orange staining, DNA fragmentation assay and transmission electron microscopic (TEM) examination. The current study demonstrated that exposure to γ-irradiation in a dose of 0.5 kGray (kGy) significantly (P < 0.05) reduced the viability of B. hominis subtype 2 by 95.2% compared to the untreated and MTZ-treated parasites (87.1%) after 48 h incubation. Combining the same dose of irradiation (0.5 kGy) with MTZ yielded a viability reduction of 94.2% and 94% after 24 and 48 h respectively, which were statistically significant (P < 0.05) compared to MTZ alone. Moreover, our results showed features of programmed cell death in the form of morphological, biochemical, and molecular changes (TEM abnormalities, caspase-like activity, and DNA fragmentation, respectively) with the high doses of γ-irradiation (0.3 and 0.5 kGy) either singly or combined with MTZ. In conclusion, cytotoxic γ-irradiation plays an important role in the inactivation of Blastocystis spp., so, it can be a promising prophylactic water-sterilizing tool against blastocystosis.
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Antineoplásicos , Antiprotozoarios , Infecciones por Blastocystis , Blastocystis hominis , Blastocystis , Antineoplásicos/farmacología , Antiprotozoarios/uso terapéutico , Apoptosis , Infecciones por Blastocystis/parasitología , Caspasas , Heces/parasitología , Humanos , Metronidazol/farmacologíaRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a major health concern. Endoplasmic reticulum (ER) stress, inflammation, and metabolic dysfunctions may be targeted to prevent the progress of nonalcoholic fatty liver disease. Sulforaphane (SFN), a sulfur-containing compound that is abundant in broccoli florets, seeds, and sprouts, has been reported to have beneficial effects on attenuating metabolic diseases. In light of this, the present study was designed to elucidate the mechanisms by which SFN ameliorated ER stress, inflammation, lipid metabolism, and insulin resistance - induced by a high-fat diet and ionizing radiation (IR) in rats. In our study, the rats were randomly divided into five groups: control, HFD, HFD + SFN, HFD + IR, and HFD + IR + SFN groups. After the last administration of SFN, liver and blood samples were taken. As a result, the lipid profile, liver enzymes, glucose, insulin, IL-1ß, adipokines (leptin and resistin), and PI3K/AKT protein levels, as well as the mRNA gene expression of ER stress markers (IRE-1, sXBP-1, PERK, ATF4, and CHOP), fatty acid synthase (FAS), peroxisome proliferator-activated receptor-α (PPAR-α). Interestingly, SFN treatment modulated the levels of proinflammatory cytokine including IL-1ß, metabolic indices (lipid profile, glucose, insulin, and adipokines), and ER stress markers in HFD and HFD + IR groups. SFN also increases the expression of PPAR-α and AMPK genes in the livers of HFD and HFD + IR groups. Meanwhile, the gene expression of FAS and CHOP was significantly attenuated in the SFN-treated groups. Our results clearly show that SFN inhibits liver toxicity induced by HFD and IR by ameliorating the ER stress events in the liver tissue through the upregulation of AMPK and PPAR-α accompanied by downregulation of FAS and CHOP gene expression.
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Estrés del Retículo Endoplásmico , Insulinas , Isotiocianatos , Enfermedad del Hígado Graso no Alcohólico , Sulfóxidos , Proteínas Quinasas Activadas por AMP/genética , Animales , Citocinas/metabolismo , Dieta Alta en Grasa , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Ácido Graso Sintasas/farmacología , Glucosa/metabolismo , Insulinas/genética , Insulinas/metabolismo , Insulinas/farmacología , Isotiocianatos/farmacología , Isotiocianatos/uso terapéutico , Leptina , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Receptores Activados del Proliferador del Peroxisoma/genética , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Activados del Proliferador del Peroxisoma/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Ratas , Resistina/genética , Resistina/metabolismo , Resistina/farmacología , Sulfóxidos/farmacología , Sulfóxidos/uso terapéutico , Regulación hacia ArribaRESUMEN
Morphological control of the layers within the bulk heterojunction organic photovoltaics (BHJ-OPVs) is a key feature that governs their performance. In the present work, we demonstrate that zinc oxide-ZnO-interlayers sprayed via the intermittent spray pyrolysis technique, employing a low-concentration precursor solution, can yield inverted BHJ-OPVs as efficient as the standard reported ones using the conventional laboratory-scale spin-coating technique. However, we record a pioneer stability behavior of the fabricated inverted fullerene organic photovoltaics (iF-OPVs) with various sprayed ZnO conditions. Thus, after optimizing the sprayed ZnO interfacial layer morphology for the inverted PTB7-Th:PC70BM devices, by carefully inspecting the interdependence between the sprayed ZnO thin film morphology and the figures of merit of the optimized iF-OPVs, we conducted a distinct analysis on the optical and electronic properties of the fresh and degraded devices using external quantum efficiency measurements and impedance spectroscopy. Hence, we showed that the most proper ZnO microstructural morphology was obtained by spraying 25 running cycles (25R). Remarkably, we observed that 25R-ZnO-based iF-OPV devices showed a stunning stability behavior and maintained 85% of their initial power conversion efficiency even after 16.7 months without encapsulation in a dry nitrogen glovebox, demonstrating an excellent shelf stability. Accordingly, this approach might facilitate the scalability of inverted OPVs for industrial production visibility.
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BACKGROUND: Bisphenol (BPA) and ionizing radiation exposure (IR) are potent oxidants that cause free radical induction, leading to signaling pathway activation that alters cell growth. Due to the insufficient knowledge of the impact of BPA and IR on the lungs, the current study determined the impact of BPA and IR on the lung tissue of adult female Wistar rats. METHODS: Forty Wister female rats were used in this study and were randomly divided into four groups. The rats received BPA (150 mg/kg body weight/day for 6 weeks) and were exposed to IR at 2 Gy/week up to 12 Gy for 6 weeks. RESULTS: It was found that BPA and IR possess a harmful effect on the lungs via induction of oxidative stress, confirmed by increasing levels of malondialdehyde (MDA), nitric oxide, myeloperoxidase (MPO), and lactate dehydrogenase (LDH). Exposure to BPA and IR activates inflammatory cytokines TNF-α, IL-6, IL-1ß, growth factors such as TGF-ß, and gastrin-releasing peptides. BPA/IR exposures induced phosphorylated expression p-ERK1/2 and p-MEK1/2 associated with triggering of the GPER/EGFR/KRAS signaling factors, resulting in matrix metalloproteinase-2 and 9 overexpression and the development of lung tumors. Our findings support the causal role of two deleterious environmental pollutants BPA and IR, via the cytotoxicity in the respiratory system in the form of severe lung damage resulting in cancerous cells.
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Sistema de Señalización de MAP Quinasas , Metaloproteinasa 2 de la Matriz , Animales , Carcinogénesis , Receptores ErbB , Femenino , Incidencia , Pulmón , Proteínas Proto-Oncogénicas p21(ras) , Ratas , Ratas Wistar , Transducción de SeñalRESUMEN
Cancer stem cells (CSCs) are implicated in the genesis, development, and recurrence of lung cancer (LC) with great resistance to radiation and chemotherapy. The aim of this study is to assess the inhibitory potential of ethanol extract of Withania somnifera (WS); 500 mg/kg body-weight/day and 8 Gy of ionizing radiation (IR) could inhibit the stemness gene and confer the radiosensitizing effect of W. somnifera extract in the female rat LC model. Compared to IR or WS, the in vitro assay showed that WS + IR potentiates proliferation-inhibition and cell death of the A-549 cell line and suppresses sphere formation. The Hedgehog (Hh) signaling associated with the expression levels of lung CSC markers, octamer-binding transcription factor-4 (OCT4), SRY-box 2 (SOX2), CD133, ATP Binding Cassette Subfamily G Member 2 (ABCG2), and NANOG was upregulated with stimulated epithelial-to-mesenchymal transition (EMT) indicators α-smooth muscle actin (α-SMA), Drosophila embryonic protein (SNAIL-1), Vimentin, and E-cadherin in the LC rat model. The W. somnifera extract plus IR inhibits Hh activation factors, which has resulted in the suppression of CSC gene markers and EMT factors. W. somnifera extract may be a significant adjuvant in the course of radiotherapy, contributing to the termination of tumor progression, and thus providing cure insights into the molecular mechanisms of lung CSCs intervention.
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Bisphenol-A (BPA) and gamma-radiation are two risky environmental pollutants that human beings are exposed to in everyday life and consequently they threaten human health via inducing oxidative stress, inflammation, and eventually tissue damage. This study aims at appraising the protective effect of Boswellic Acid (BA) (250 mg/kg/day, orally) administration on BPA (150 mg/kg/day, i.p) and γ-irradiation (IR) (3 Gy/week for 4 weeks up to cumulative dose of 12 Gy/experimental course) for 4 weeks-induced damage to liver and heart tissues of rats. The present results indicated a significant improvement against damage induced by BPA and IR revealed in biochemical investigations (hepatic PPAR-α/P38 and cardiac ET-1/Calcineurin-A/NFATc1/P38) and histopathological examination of liver and heart. It could be concluded that BA possesses a protective effect against these two deleterious environmental pollutants which attracted major global concerns due to their serious toxicological impact on human health.
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Calcineurina , Hígado Graso , PPAR alfa , Triterpenos , Remodelación Ventricular , Animales , Compuestos de Bencidrilo/efectos adversos , Calcineurina/metabolismo , Contaminantes Ambientales/efectos adversos , Hígado Graso/inducido químicamente , Hígado Graso/tratamiento farmacológico , Rayos gamma/efectos adversos , Hígado/metabolismo , Estrés Oxidativo , PPAR alfa/metabolismo , Fenoles/efectos adversos , Ratas , Factores de Transcripción/metabolismo , Triterpenos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Metabolic shifting from mitochondrial respiration to glycolysis characterizes malignant cells from its normal counterparts and is attributed to overactivation of oncogenic signaling pathways. Hence, this study intended to investigate the influence of canagliflozin (CAN) and/or γ-irradiation (γ-IR) on HepG2 cell proliferation, crosstalk between phosphatidylinositol 3-kinases (PI3K)/AKT/glycogen synthase kinase-3-ß (GSK3-ß)/mTOR and Wnt/ß-catenin signaling pathways, and their regulation of diverse processes, such as endoplasmic reticulum (ER) stress, autophagy, and apoptosis. MATERIALS AND METHODS: HepG2 cells were treated with different doses of CAN and then exposed to different doses of γ-IR to achieve optimization that was based on cytotoxicity and clonogenic assays, respectively. The effects of CAN and/or γ-IR on glycolytic metabolism, cellular bioenergetics, oxidative stress, ER stress and autophagy biomarkers, expression of PI3K/AKT/GSK3-ß/mTOR and Wnt/ß-Catenin signaling pathways, and apoptotic markers were monitored. RESULTS: CAN enhanced the antitumor potential of γ-IR as displayed by a significant inhibition of clonogenic survival in HepG2 cells via inhibition of glucose uptake, lactate release, and modulation of ER stress-mediated autophagy; switched it to apoptosis; as well as disabled signaling pathways which contribute to metabolic reprogramming and tumor progression induced by γ-IR that confer radioresistance and treatment failure. CONCLUSION: Our study sheds light on the effective combination of CAN and γ-IR in hepatocellular carcinoma treatment and necessitates CAN treatment prior to γ-IR to overcome metabolic reprogramming-associated radioresistance and improve curative outcomes.
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Autofagia , Canagliflozina/farmacología , Carcinoma Hepatocelular/patología , Estrés del Retículo Endoplásmico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Neoplasias Hepáticas/patología , Apoptosis , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Proliferación Celular , Quimioradioterapia , Rayos gamma , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Proteína Wnt1/genética , Proteína Wnt1/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Living organisms respond to physical, chemical, and biological threats with a potent inflammatory response which alters organ cell signaling and leads to dysfunction. We evaluated the therapeutic effect of bone marrow-based mesenchymal stromal cell (BM-MSC) transplanted in rats to preserve tissue integrity and to restore homeostasis and function in the pancreatitis experimental pattern. METHODS: This study involved 40 adult male Wister rats. Repeated L-arginine injections caused chronic pancreatitis (CP), leading to the development of pancreatic damage and shifting the intracellular signaling pathways. Rats were then infused with BM-MSC labeled with PKH26 fluorescent linker dye for 12 weeks. RESULTS: Cell-surface indicators of BM-MSCs such as CD 90 and CD29 were expressed with the lack of CD34 expression. BM-MSC treatment considerably improved the alterations induced in a series of inflammatory markers, including IL-18, TNF-α, CRP, PGE2, and MCP-1. Furthermore, improvement was found in digestive enzymes and lipid profile with amelioration in myeloperoxidase activity. BM-MSC treatment also regulated the (TGF-/p-38MPAK/SMAD2/3) signaling factors that enhances repair of damaged pancreatic tissue, confirmed by reversed alteration of histopathological examination. CONCLUSION: our results further bring to light the promise of cell transplant therapy for chronic pancreatitis.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Pancreatitis Crónica/terapia , Amilasas/metabolismo , Animales , Arginina , Proteína C-Reactiva/análisis , Citocinas , Dinoprostona/sangre , Lipasa/metabolismo , Metabolismo de los Lípidos , Masculino , Páncreas/enzimología , Páncreas/patología , Pancreatitis Crónica/sangre , Pancreatitis Crónica/inducido químicamente , Pancreatitis Crónica/metabolismo , Ratas Wistar , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Liver injury due to ionizing radiation exposure either accidental or after radiotherapy treatment, may lead to many alterations in proteins expression related to inflammation or apoptosis. Our study investigated the curative effect of Mangosteen (MGS) extract (fruit rind) against ionizing radiation (IR) induced liver damage. METHODS: Hepatotoxicity was induced in Wister rats by exposure to an acute single dose (6 Gy) of IR while MGS was given orally to rats (500 mg/kg bwt) and administered daily for 30 days after irradiation. RESULTS: MGS treatment has significantly attenuated redox imbalance state and toxicity induced by protracted exposure to gamma-rays in liver tissues, which was substantiated by the significant amelioration of liver function tests, MDA contents, antioxidant enzymes (SOD and CAT) activities and NO level. MGS inhibited also the inflammatory markers (TNF-alpha, IL-6 and CRP) and downregulated transcriptional factor NF-Kappa-B/TGF-ß1. These alterations were concomitant with an improvement of the Proliferating cell nuclear antigen (PCNA) which is a protein expressed in the nuclei of cells during cell cycle and is important for both DNA synthesis and DNA repair. These results were confirmed by amelioration in histological and ultrastructural examinations. CONCLUSION: We concluded that MGS could ameliorate via minimizing significantly the amount of oxidative damage, inflammations disturbances and pro-apoptotic alternations induced by IR. MGS may be a promising supplement with protective effects from irradiation-induced injury such as TNF-α/NF-κB/TGF-ß1 management.
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Human exposure to radio-therapeutic doses of gamma rays can produce late effects, which negatively affect cancer patients' quality of life, work prospects, and general health. This study was performed to explore the role of Piceatannol (PIC) in the process of "mitochondrial biogenesis" signaling pathway as possible management of disturbances induced in stressed animal model(s) either by gamma-irradiation (IR) or administration of reserpine (RES); as a mitochondrial complex-I inhibitor. PIC (10 mg/kg BW/day; orally) were given to rats for 7 days, after exposure to an acute dose of γ-radiation (6 Gy), or after a single reserpine injection (1 g/kg BW; sc). Compared to reserpine or γ-radiation, PIC has attenuated hepatic and renal mitochondrial oxidative stress denoted by the significant reduction in the content of lipid peroxides and NO with significant induction of SOD, CAT, GSH-PX, and GR activities. PIC has also significantly alleviated the increase of the inflammatory markers, TNF-α and IL-6 and apoptotic markers, cytochrome c, and caspase-3. The decrease of oxidative stress, inflammation, and apoptotic responses were linked to a significant amelioration in mitochondrial biogenesis demonstrated by the increased expression and proteins' tissue contents of SIRT1/p38-AMPK, PGC-1α signaling pathway. The results are substantiated by the significant amelioration in mitochondrial function verified by the higher levels of ATP content, and complex I activity, besides the improvement of hepatic and renal functions. Additionally, histopathological examinations of hepatic and renal tissues showed that PIC has modulated tissue architecture after reserpine or gamma-radiation-induced tissue damage. Piceatannol improves mitochondrial functions by regulating the oxidant/antioxidant disequilibrium, the inflammatory and apoptotic responses, suggesting its possible use as adjuvant therapy in radio-therapeutic protocols to attenuate hepatic and renal injuries.
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Rayos gamma , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Protectores contra Radiación/farmacología , Reserpina , Estilbenos/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Riñón/metabolismo , Riñón/patología , Riñón/efectos de la radiación , Hígado/metabolismo , Hígado/patología , Hígado/efectos de la radiación , Masculino , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Traumatismos Experimentales por Radiación/genética , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Protectores contra Radiación/uso terapéutico , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Sirtuina 1/genética , Sirtuina 1/metabolismo , Estilbenos/uso terapéuticoRESUMEN
The kynurenine pathway (KP, IDO/Kyn pathway) is an important metabolic pathway related to many diseases. Although cranial radiotherapy is the mainstay in metastatic tumors management, its efficacy is limited owing to the associated neuropsychiatric disorders. Sildenafil (SD) and simvastatin (SV) were reported to have antioxidant/anti-inflammatory effects and to serve as NO donor/BH4 regulator, respectively. Fluoxetine (Fx) is an FDA-approved anti-depressant agent and one of the selective serotonin reuptake inhibitor drugs (SSRI), used in neurological disorder treatment. The study objective was to investigate the role of cranial irradiation (C-IR) on KP signaling impairment and the possible intervention by SD and/or SV (as nitric oxide (NO) donor/Tetrahydrobiopterin (BH4) regulatory) on KP following C-IR-induced disruption compared with Fx (as standard drug).Herein, rats were exposed to C-IR at a single dose level of 25 Gy, then treated with sildenafil (SD) and/or simvastatin (SV), and fluoxetine (Fx) at doses of 75, 20, 10 mg/kg/day, respectively. The body weight gain and forced swimming test (FST) were used for evaluation along with the biochemical quantifications of KP intermediates and histopathological examination of cortex and hippocampus. The results indicated a significant activation of KP following C-IR as manifested by decreased Trp content and increased activities of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) with a rise in kynurenine (KYN) and quinolinic acid (QA) hippocampal contents. In addition, a state of C-IR-induced oxidative stress, inflammation, NO-pathway dysregulation and neuronal apoptosis were observed as compared to the control group. However, significant modulations were recorded after the combined administration of SD and SV than those offered by each of them alone and by Fx. The biochemical assessment results were supported by the histopathological tissue examination. It could be concluded that the co-administration of SV and SD offers a neuroprotective effect against irradiation-induced brain injury due to its NO donor/BH4 regulatory activities, anti-inflammatory and antioxidant properties that modulate IDO/KYN pathway.
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Biopterinas/análogos & derivados , Lesiones Encefálicas/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Óxido Nítrico/metabolismo , Citrato de Sildenafil/uso terapéutico , Simvastatina/uso terapéutico , Animales , Antidepresivos de Segunda Generación/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Biopterinas/metabolismo , Encéfalo/patología , Encéfalo/efectos de la radiación , Lesiones Encefálicas/patología , Irradiación Craneana/efectos adversos , Depresión/tratamiento farmacológico , Fluoxetina/uso terapéutico , Rayos gamma , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Ratas , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiaciónRESUMEN
Hazard and risk associated with the use of radiotherapy play a crucial role in brain injury with interference via the neuroendocrine activity of the cancer survivors, and there is no effective preventive strategy. We conducted this study to assess the effect of citicoline in biosynthesis variants occurring in the cerebral cortex of rats in response to head γ-irradiation. Bio-analysis includes MDA, 8-OHdG, and NO as oxidation indicators; total antioxidant activity; the inflammatory factors TNF-α, IL-1ß, and amyloid-ß 42 levels; the caspase-3 cell death marker; IGF-I; serum hormones including GH, ACTH, FSH, and LH; and the neurotransmitters acetylcholine, dopamine, and serotonin. We exposed animals to 10 Gy head gamma irradiation followed by citicoline treatment and sustained for 30 days. The animals were sacrificed at the 3rd and 30th day post-irradiation. Citicoline mechanism has been linked to potent radical reduced ability counteracting the oxidative stress-mediated inflammation and apoptosis. Citicoline treatment has normalized the altering recorded in serum hormones associated with a significant modulation in the levels of IGF-1/PI3K/AKT factors. Such improvements have been concomitant with regulated neurotransmitter levels. We could conclude that citicoline may safely be supplemented to avoid both short- and long-term damages to the neuroendocrine disturbances, oxidative stress, inflammation, and apoptosis induced by head irradiation.
Asunto(s)
Lesiones Encefálicas , Citidina Difosfato Colina , Animales , Apoptosis , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas , RatasRESUMEN
Hepatitis was characterized by extreme inflammation and hepatocellular damage. Therefore, the current study aimed to gain insights into the modulation role of Cinnamic acid nanoparticles (CANPs) against acute hepatitis induced by d-Galactosamine and gamma radiation exposure (D-Gal/radiation) in the rat model and to suggest the implied molecular mechanism of CANPs. Acute hepatitis seriousness and the serum enzyme activities of ALT, AST, and ALP have been diminished upon oral administration of CANPs. Besides, the hepatic tissue levels of malondialdehyde (MDA) and nitric oxide (NO) have been significantly decreased, and the total antioxidant activity (TAO) depletion was extremely restored. Furthermore, the reduction of hepatic damage caused by pretreatment with CANPs was accompanied by significant suppression in the levels of hepatic proinflammatory cytokines (TNF-α, IL-1ß, and IL-18), NF-κB, NLRP3, caspase-1 and proapoptotic protein BAX whereas anti-apoptotic protein Bcl-2 level significantly elevated as compared with D-Gal/radiation-induced acute hepatitis (AH) group. Also, CANPs suppress the D-Gal/radiation-induced IL-1ß, IL-18, and ASK1 mRNA gene expression and the protein expression of TLR4 and MyD88 in the hepatic tissue. These biochemical parameters are confirmed by histological examination of the liver tissues. The present results indicated that CANPs can protect the hepatic cells from damage by both its anti-inflammatory and antioxidant influence as well as by modulating oxidation cellular pathways that have contributed to the acute severity of hepatitis. Also, CANPs is capable of suppressing apoptosis. Consequently, Nanoparticles of Cinnamic acid have the medicinal ability to protect the liver from acute hepatitis.
Asunto(s)
Antiinflamatorios/uso terapéutico , Cinamatos/uso terapéutico , Hepatitis/tratamiento farmacológico , Nanopartículas/uso terapéutico , Enfermedad Aguda , Animales , Antiinflamatorios/química , Antiinflamatorios/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Cinamatos/química , Cinamatos/toxicidad , Galactosamina , Rayos gamma , Hepatitis/patología , Hígado/patología , Hígado/efectos de la radiación , Masculino , Nanopartículas/química , Nanopartículas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Proteínas/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: Chronic Pancreatitis (CP) is a multifactorial disease. It was characterized by severe inflammation and acinar cell destruction. Thus, the present study was initiated to evaluating the ability of bone marrow-based mesenchymal stem cell (MSCs) combined with Icariin to restore and regenerate acinar cells in the pancreas of rats suffering chronic pancreatitis. METHODS: Chronic pancreatitis was induced in rats via both L-arginine plus radiation, repeated L-arginine injection (2.5g/Kg body-weight, 1, 4,7,10,13,16,19 days), then, on day 21, rats were exposed to a single dose of gamma-radiation (6 Gy), which exacerbate injury of pancreatic acinar cells. One day after irradiation, rats were treated with either MSCs (1 × 107 /rat, once, tail vein injection) labeled PKH26 fluorescent linker dye and/or Icariin (100 mg/Kg, daily, orally) for 8 weeks. RESULTS: Icariin promotes MSCs proliferation boosting its productivity in vitro. MSCs, and/or icariin treatments has regulated molecular factors TGF-ß/PDGF and promoted the regeneration of pancreatic tissues by releasing PDX-1 and MafA involved in the recruitment of stem/progenitor cell in the tissue, and confirmed by histopathological examination. Moreover, a significant decrease in IL-8 and TNF-α cytokines with significant amelioration of myeloperoxidase activity were noted. As well as, reduction in MCP-1 and collagen type-1 levels along with Hedgehog signaling down-regulating expression in such cells, Patched-1, Smoothened, and GLi-1. CONCLUSION: The potent bioactive therapeutic Icariin combined with MSCs induces a significantly greater improvement, compared to each therapy alone.
RESUMEN
BACKGROUND: Although intrauterine contraceptive device is highly effective, safe, long term and reversible method of contraception, the general population and physicians refuse. IUDs for nulliparous women due to persistent rumors about its side effects and complications. The aim of this study was to assess the acceptability of IUD use in nulliparous women by both women and health care providers in Egypt. METHODS: Five hundred thirty nulliparous women and 200 physicians were interviewed in 10 family planning clinics in Suez and Minia cities - Egypt. The knowledge and attitudes of women and health care providers towards IUD use in nulliparous women were assessed through a well designed questionnaire over 2 years. Those women who accepted using IUD were then followed up for 6 months. RESULTS: Most of nulliparous women sought for contraception reported a negative impression of IUD method (96.2%). 82.5% of physicians had the same attitude. The reasons for refusing IUD among nulliparous women are fear of side effects including infection (52.8%), and bleeding (37.7%).Also, fear of subsequent infertility 51.9% of women. Regarding the providers, increased pelvic inflammatory disease (PID) represented the highest percentage (70%) for non acceptability, followed by difficult insertion (52.5%). Ninety women who accepted use IUD were followed up 6 months later, 94.4% were still using the method and77.8% were happy with the results. CONCLUSION: The main barriers that hinder the use of IUD in nulliparous women are the women insufficient knowledge and attitude of their physicians. Good client counseling. Good training for physician to improve their experience would help increase the use of such effective and safe method.
Asunto(s)
Actitud del Personal de Salud/etnología , Conocimientos, Actitudes y Práctica en Salud/etnología , Personal de Salud/psicología , Dispositivos Intrauterinos/estadística & datos numéricos , Aceptación de la Atención de Salud/etnología , Adolescente , Adulto , Anticoncepción , Estudios Transversales , Egipto , Miedo , Femenino , Personal de Salud/estadística & datos numéricos , Humanos , Entrevistas como Asunto , Dispositivos Intrauterinos/efectos adversos , Persona de Mediana Edad , Paridad , Aceptación de la Atención de Salud/psicología , Enfermedad Inflamatoria Pélvica , Embarazo , Adulto JovenRESUMEN
In this work Polyaniline (PANI) fiber has been synthetized by the interfacial polymerization method. The thermal behavior of graphene - multiwall carbon nanotubes (MWCNs) composite material (C-Mix) blended with PANI fiber was investigated. Graphene was prepared by thermal reduction of the fabricated graphene oxide (GO) using modified Hummers' method. SEM measurement reveals that MWCNTs were well organized within 2D large surface area graphene nano-sheets to form 3D carbon-base hierarchical structure, and PANI was mixed as a binder polymer matrix. Structural measurements confirm the formation of wide area graphene sheets with crumples, wrinkles, and folds around the edges. Transmission electron microscopy (TEM) images agreed with the well distribution of CNTs within graphene nano-sheets. Also, the surface morphology of the synthesized composites has a spherical regular agglomeration of PANI granular structure on wide area graphene nano sheets with CNT embedded. The change in the existed phonon modes of the fabricated nano-composite was analyzed using Raman spectroscopy. Moreover, Seebeck coefficient changes from +132.4 µV/K to -10.3 µV/K after adding carbon-based materials which reflects the reverse of predominate carriers by doping PANI with carbon-based material. It has been noticed that there is an enhancement of thermal conductivity of the fabricated composite with respect to neat polymer. Hence, we propose that 3D carbon structure with PANI construct a stable N-Type thermoelectric material.