RESUMEN
Aim: Leukemia is a malignant clonal illness stem from the mutations of hematopoietic cells. Acute lymphoblastic leukemia is one of the utmost prevalent kinds of leukemia, is brought on by atypical lymphoid progenitor cell division in the bone marrow. Materials & methods: A comparative study between, titanium Nanoparticle-loaded doxorubicin or cisplatin and lactoferrin-loaded doxorubicin or cisplatin, on 7,12-dimethylbenz[a]-anthracene (DMBA)-induced leukemia was investigated and confirming the hypothesis that messenger RNA of Hprt/K-RAS/c-Myc/SAT-2/P53/JAK-2 is a forthcoming signaling pathways in leukemia. Results: A significant alteration in Hprt, K-RAS, C-Myc, P53, JAK-2 and SAT-2 genes was observed post DMBA intoxication the aforementioned Nanodrugs modulated these signaling pathways. Conclusion: The carrier-loaded drugs triggered cytotoxicity of cancer cells via enhancing drug efficacy and bio-availability.
Leukemia is the abnormal growth of white blood cells that is responsible for fighting infection. Cisplatin and doxorubicin are commonly used anticancer drugs that can combat leukemic cells however they faced some problems of poor solubility and toxicity to normal cells. Thus we designed nanodrugs as Ti-NPs-cisplatin or DOX and lactoferrin-cisplatin or DOX and compared them with DOX and cisplatin and studied their impact on DMBA-induced leukemia in rat models. Monitoring apoptotic and cell survival genes was performed. Treatment with the nanodrugs could be promising in targeting cancer cells and improving drug bio-availability thus inducing cancer cell death.
RESUMEN
Aim: To clarify the alternation of gene expression responsible for resistance of Adriamycin (ADR) in rats, in addition to investigation of a novel promising drug-delivery system using titanium dioxide nanoparticles loaded with ADR (TiO2-ADR). Method: Breast cancer was induced in female Sprague-Dawley rats, followed by treatment with ADR (5 mg/kg) or TiO2-ADR (2 mg/kg) for 1 month. Results: Significant improvements in both zinc and calcium levels were observed with TiO2-ADR treatment. Gene expression of ATP-binding cassette transporter membrane proteins (ABCA1 & ABCG1), P53 and Jak-2 showed a significant reduction and overexpression of the C-myc in breast cancer-induced rats. TiO2-ADR demonstrated a notable ability to upregulate these genes. Conclusion: TiO2-ADR could be a promising drug-delivery system for breast cancer therapy.
The current study aimed to investigate a novel and promising drug-delivery system to overcome the resistance problem by loading Adriamycin (ADR) into titanium dioxide nanoparticles (TiO2). The study also aimed to clarify the changes in gene expression responsible for the development of ADR resistance, in a rat model. First, animals were divided into four groups of ten each. Breast cancer was induced in female Sprague-Dawley rats by administering two doses of DMBA (50 and 25 mg/kg), followed by treatment with ADR at a dose of 5 mg/kg for 1 month, or TiO2-ADR at a dose of 2 mg/kg for 1 month. Biochemical and molecular analyses were conducted. Zinc and calcium levels were found to significantly decrease after cancer induction. Treatment with ADR alone or in combination with TiO2 showed a significant improvement in both mineral levels, with the TiO2-ADR group showing superior results. Gene expression of ATP-binding cassette transporter membrane proteins (ABCA1 & ABCG1), P53 and Jak-2 showed a significant decrease after DMBA-induced breast cancer. However, both the ADR- and TiO2-ADR-treated groups showed a notable increase in gene expression, with the TiO2-ADR group showing the highest increase. On the other hand, there was a significant overexpression of the C-myc gene after DMBA-induced breast cancer. However, both ADR and TiO2-ADR treatments resulted in a notable decrease in C-myc gene expression. Based on the data, TiO2-ADR could be a promising drug-delivery system for breast cancer therapy.
RESUMEN
This study investigates the viscoelastic deformation mechanisms of bone as a response to Vickers hardness indentation. We utilized advanced high-resolution scanning electron microscopy (SEM) to investigate a distinct deformation pattern that originates from the indentation site within the bone matrix. The focus of our research was to analyze a unique deformation mechanism observed in bone tissue, which has been colloquially termed as "screw-like" due to its resemblance to a screw thread when viewed under an optical microscope. The primary goals of this research are to investigate the distinctive characteristics of the "screw-like" deformation pattern and to determine how the microstructure of bone influences the initiation and control of this mechanism. These patterns, emerging during the dwell period of indentation, underscore the viscoelastic nature of bone, indicating its propensity for energy dissipation and microstructural reconfiguration under load. This study uncovered a direct correlation between the length of the "screw-like" deformation and the duration of the indentation dwell time, providing quantifiable evidence of the bone's viscoelastic behavior. This finding is pivotal in understanding the mechanical properties of bone, including its fracture toughness, as it relates to the complex interplay of factors such as energy dissipation, microstructural reinforcement, and stress distribution. Furthermore, this study discusses the implications of viscoelastic properties on the bone's ability to resist mechanical challenges, underscoring the significance of viscoelasticity in bone research.
RESUMEN
The effects of post heat treatment atmosphere on microstructure and corrosion resistance of duplex stainless steel welded joints were investigated. Post weld heat treatment (PWHT) was carried out with and without protective atmospheres. Nitrogen and argon are used as protective gases individually. Detailed microstructure examination (optical and SEM) demonstrates that nitrides precipitates are highly observed in the welded zones for nitrogen protected samples. An observed drop of ferrite volume fraction in post weld heat treated samples compared with welded samples without heat treatment leading to corrosion resistance enhancement of heat treated welded joints. An exception for using nitrogen as heat treatment atmosphere a decreased corrosion resistance of weldments is investigated due to nitride precipitates. An increase in the weld zone hardness for post weld heat treated samples compared with base alloy. The initial hardness of duplex stainless steel was 286 Hv while average hardness of weld zone was 340, 411, 343, and 391 Hv for as welded, PWHT using air, argon, and nitrogen atmospheres, respectively. Weld zone hardness increased to 33, 44, 20, and 37%. A significant decrease in the ultimate tensile strength and elongation after PWHT. The initial Ultimate tensile strength duplex stainless steel base material was 734.9 MPa while Ultimate tensile strength of the welded joints was 769.3, 628.4, 737.8, and 681.4 MPa for the following conditions: as welded, PWHT using air, argon, and nitrogen atmospheres, respectively.
RESUMEN
Triple-negative breast cancer is one of the most aggressive breast cancer. The first therapeutic option is chemotherapy, often based on anthracycline as doxorubicin. However, chemotherapy efficacy is limited in by the presence of P-glycoprotein (Pgp), a membrane transporter protein that effluxes doxorubicin, reducing its cellular accumulation and toxicity. Inhibiting Pgp activity with effective and non-toxic products is still an open challenge. In this work, we demonstrated that the natural product Glabratephrin (Glab), a prenylated flavonoid from Tephrosia purpurea with a unique chemical structure, increased doxorubicin accumulation and cytotoxicity in triple negative breast cancer cells with high levels of Pgp, characterized by both acquired or intrinsic resistance to doxorubicin. Glab also reduced the growth of Pgp-expressing tumors, without adding significant extra-toxicities to doxorubicin treatment. Interestingly, Glab did not change the expression of Pgp, but it reduced the affinity for Pgp and the efflux of doxorubicin, as suggested by the increased Km and the reduced Vmax. In silico molecular docking predicted that Glab binds two residues (phenylalanine 322, glutamine 721) localized in the transmembrane domains of Pgp, facing the extracellular environment. Moreover, site-directed mutagenesis identified glycine 185 as a critical residue mediating the reduced catalytic efficacy of Pgp elicited by Glab. We propose Glab as an effective and safe compound able to reverse doxorubicin resistance mediated by Pgp in triple negative breast cancers, opening the way to a new combinatorial approach that may improve chemotherapy efficacy in the most refractory and aggressive breast cancer.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Flavonoides/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Doxorrubicina/farmacología , Femenino , Flavonoides/farmacología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones Endogámicos BALB C , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
Diabetes is considered one of the most important health emergencies worldwide and Egypt has 8.2 million diabetic patients according to the International Diabetes Federation report in 2017. The objective of this study was to monitor the time-course variation in the metabolic profile of diabetic rats to detect urinary metabolic biomarkers using the metabolomics approach. Type 2 diabetes was induced in male Wistar albino rats using a single intraperitoneal injection of 40 mg/kg of streptozotocin following oral administration of 10% fructose in drinking water for 3 weeks. Then, urine was collected for 24 h from rats at three time points (0, 2, and 4 weeks after confirmation of diabetes), and were analyzed by nuclear magnetic resonance (H1 -NMR), followed by multivariate data analysis. The results from H1 -NMR pointed out that d-glucose, taurine, l-carnitine, l-fucose, 1,5-anhydrosorbitol, and d-galactose levels showed consistent significant variation (p < 0.05) between the positive (diabetic) and negative (normal) controls during the whole experimental period. Also, with the disease progression, myoinositol, and l-phenylalanine levels were significantly altered (p < 0.05) after 2 weeks and this alteration was maintained till the end of the 4-week experimental period in the positive control group. From the results of the present study, it could be concluded that we cannot depend only on glucose levels for prognostic purposes since there are other metabolic disturbances in diabetes which need to be tracked for better disease prognosis.
Asunto(s)
Diabetes Mellitus Experimental/orina , Glucosuria/orina , Metabolómica/métodos , Animales , Biomarcadores/orina , Carnitina/orina , Análisis por Conglomerados , Desoxiglucosa/orina , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Progresión de la Enfermedad , Fructosa/administración & dosificación , Fucosa/orina , Galactosa/orina , Glucosuria/inducido químicamente , Glucosuria/genética , Glucosuria/patología , Inositol/orina , Espectroscopía de Resonancia Magnética , Masculino , Metaboloma , Fenilalanina/orina , Ratas , Ratas Wistar , Estreptozocina/administración & dosificación , Taurina/orina , Factores de TiempoRESUMEN
Posidonia oceanica is a sea grass belonging to the family Posidoniaceae, which stands out as a substantial reservoir of bioactive compounds. In this study, the secondary metabolites of the P. oceanica rhizome were annotated using UPLC-HRESI-MS/MS, revealing 86 compounds including simple phenolic acids, flavonoids, and their sulphated conjugates. Moreover, the P. oceanica butanol extract exhibited substantial antioxidant and antidiabetic effects in vitro. Thus, a reliable, robust drug delivery system was developed through the encapsulation of P. oceanica extract in gelatin nanoparticles to protect active constituents, control their release and enhance their therapeutic activity. To confirm these achievements, untargeted GC-MS metabolomics analysis together with biochemical evaluation was employed to investigate the in vivo anti-diabetic potential of the P. oceanica nano-extract. The results of this study demonstrated that the P. oceanica gelatin nanoparticle formulation reduced the serum fasting blood glucose level significantly (p < 0.05) in addition to improving the insulin level, together with the elevation of glucose transporter 4 levels. Besides, multivariate/univariate analyses of the GC-MS metabolomic dataset revealed several dysregulated metabolites in diabetic rats, which were restored to normalized levels after treatment with the P. oceanica gelatin nanoparticle formulation. These metabolites mainly originate from the metabolism of amino acids, fatty acids and carbohydrates, indicating that this type of delivery was more effective than the plain extract in regulating these altered metabolic processes. Overall, this study provides novel insight for the potential of P. oceanica butanol extract encapsulated in gelatin nanoparticles as a promising and effective antidiabetic therapy.
RESUMEN
Bone is a nanocomposite material where the hard inorganic (hydroxyapatite crystallites) and organic (collagen fibrils) components are hierarchically arranged in the nanometer scale. Bone quality is dependent on the spatial distributions in the shape, size and composition of bone constituents (mineral, collagen and water). Bone hardness is an important property of bone, which includes both elastic and plastic deformation. In this study, a microhardness test was performed on a deer bone samples. The deer tibia shaft (diaphysis) was divided into several cross-sections of equal thickness; samples were prepared in untreated, boiled water treatment (100 °C for 30 min) and sodium hypochlorite (NaOCl) treatment conditions. Microhardness tests were performed on various regions of the tibial diaphysis to study the heterogeneous characteristics of bone microhardness and highlight the role of the organic matrix in bone hardness. The results indicated that boiled water treatment has a strong negative correlation with bone hardness. The untreated bone was significantly (+20%) harder than the boiled-water-treated bone. In general, the hardness values near the periosteal surface was significantly (23 to 45%) higher than the ones near the endosteal surface. Samples treated with NaOCl showed a significant reduction in hardness.
RESUMEN
Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI3K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in hepatocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy.
RESUMEN
OBJECTIVES: Type 2 diabetes mellitus (DMT2) is contributed to dual interactions between environmental factors and certain genetic factors. This impressed a great need for novel treatment strategy. Nevertheless, Hyssopus officinalis (H. officinalis) as a terrestrial herb is considered to be an important source of natural antioxidants, it could be assessed as an anti-hyperglycemic agent. METHODS: In the current study, HPLC identified the active constitutes of H. officinalis, including total polyphenols, and flavonoids. Type 2 diabetes mellitus was induced in male Wistar albino rats via a single ip dose of streptozotocin (STZ) (35 mg/kg BW). One week post diabetes induction, rats were administrated H. officinalis (500 mg/ kg BW) orally for one month. Molecular analysis was assessed to investigate the efficiency of H. officinalis on modulating ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) genes, in addition to apoptotic biomarkers, glycogen synthase kinase-3ß (GSK-3ß) and cellular oncogene-fos (C-fos) genes. Furthermore, inflammatory biomarkers, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) gene expression were also assessed. RESULTS: H. officinalis alcoholic extract declared the presence of polyphenols as gallic acid and flavonoids as quercetin in addition to many active constituents. Apigenin-7-glucoside and Chlorgenic acid were the most common constituents in the extract. RT-PCR results declared a significant up-regulation in mRNA gene expression of ABCA1 and ABCG1 upon H. officinalis treatment. Meanwhile, C-fos gene expression recorded a slight down-regulation. Gene expression of apoptotic biomarker GSK-3ß demonstrated a significant down regulation as well as inflammatory biomarkers NF-κB and TNF-α. CONCLUSION: From the data recorded, it could be concluded that H. officinalis exerts a great hypoglycemic potential via modulating C-fos, GSK-3ß, NF-κB, TNF-α, ABCA1 and ABCG1 gene expression and signaling pathways and could be considered as an effective candidate for DMT2 treatment.
RESUMEN
Objective: The aim of the present work is to evaluate the toxicity of titanium dioxide nanoparticles (TiO2NPs) according to their doses and particle sizes. Materials and methods: The effect of five days oral administration of TiO2NPs (21 and 80 nm) with different doses (50, 250 and 500 mg/kg body weight) was assessed in mice via measurement of oxidative stress markers; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO), liver function indices; aspartate and alanine aminotransferases (AST and ALT), chromosomal aberrations and liver histopathological pattern. Results: The results revealed drastic alterations in all the measured parameters and showed positive correlation with the gradual dose increment. In addition, the smaller particle size of TiO2NPS (21 nm) had more adverse effect in all the selected biochemical parameters, genetic aberrations and histological investigations. Conclusions: Toxicity of TiO2NPs increases in a dose-dependent manner and vice versa with particles size. The evaluated biomarkers are good indicators for TiO2NPs toxicity. More detailed studies are required before the recommendation of TiO2NPS as food additives.
Asunto(s)
Biomarcadores/sangre , Nanopartículas/toxicidad , Titanio/toxicidad , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Catalasa/sangre , Aberraciones Cromosómicas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glutatión/sangre , Hígado/metabolismo , Hígado/patología , Malondialdehído/sangre , Ratones , Nanopartículas/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Superóxido Dismutasa/sangre , Titanio/metabolismoRESUMEN
The expedient fungi Candida albicans (C. albicans) is able to thrive in many host niches including blood stream, skin, mucosal surfaces, and different body organs. Herein, the assessment of novel synthesized pyrimidine derivatives as anti fungal agent was investigated. Female albino mice were injected intraperitoneally by C. albicans (1.5 × 106 CFU). infected Mice then subjected to treatment with two different doses which was low (50 mg/kg) and high one (200 mg/kg) of diflucan in addition to the newly synthestic compounds (2-(4- (Pyridine- 2- yl) aminosulfonyle phenylamino) - 6 -(naphthalene-2- yl)-4-(pyridine-2- yl) n - 3 carbonitril) and (2-(4-(Pyrimidine-2- yl) aminosulfonyle phenylamino)- 6 -(naphthalene-2- yl)- 4 -(pyridine-2- yl) pyridine-3- carbonitril) donated as (C1 & C2, respectively). Three weeks later gene expression of renal alpha smooth muscle actin (α-SMA) and of cyclooxygenase-2 (COX-2) protein expression were assessed as well as serum malondialdehyde (MDA) and total antioxidant capacity in both kidney and brain tissues. Furthermore, acetylcholinestrase activity was assessed. Candida albicans significantly elevated serum MDA. On the other hand, C. albicans injection revealed a significantly reduction in total antioxidant capacity in kidney as well as in brain tissue. Furthermore, acetylcholine assessment declared a significant elevation. All biochemical parametersÛ¥ upset were modulated upon new synthesized compounds treatment. Molecular analyses declared a significant down - regulation in renal α -smooth muscle actin gene expression in addition to, a significant down- regulation in COX-2 protein expression. From data recorded, it could be concluded that, C2 in a dose 200 mg ∕kg noticeably declared a significant effect comparing with the other treated groups revealing its promising effect as anti-fungal agent.
RESUMEN
Non-alcoholic fatty liver disease is a leading cause of chronic liver disease in western countries. The current study aimed to detect and evaluate lipidomic biomarkers for early detection of NAFLD as well as the potential efficiency of methanolic extract of Eclipta prostrata (E. prostrata) on disease management. In this study, Phytochemical screening of E. prostrata methanolic extract was performed using HPLC. NAFLD was induced in albino rats using a high-fat diet together with cholesterol and cholic acid. Comprehensive lipidomic analyses on sera from rats bearing NAFLD as well as normal healthy animals were carried out based on GCMS and multivariate data analysis. The results showed that high doses (300&200â¯mg/kg.BW) of E. prostrata extract exhibited significant improvement in liver enzymes (ALT & AST) and lipid profile [total cholesterol (TC), triacylglycerides (TAGs), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C)] in rats bearing NAFLD. Glycerol, linoleic acid, arachidonic acid and cholest-5-en-3-ol (3ß) acetate were detected as lipidomic biomarkers for early detection of NAFLD in rats' sera. Furthermore, E. prostrata extract showed a significant amelioration in the levels of these metabolic biomarkers in both protective and treated groups. These finding devoutly recommend using of lipidomic biomarkers for early detection of NAFLD and E. prostrata could be used as a protective agent as well as ameliorate this disease through its probable action on the fore-mentioned metabolites.
Asunto(s)
Eclipta/química , Lípidos/sangre , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Biomarcadores/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas/métodos , Masculino , Análisis Multivariante , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Extractos Vegetales/administración & dosificación , Ratas , Ratas WistarRESUMEN
A polysaccharide characterized as galactomannan (GMann) with a molecular weight of 117.76 kDa was isolated from the aqueous extract of Caesalpinia gilliesii (C. gilliesii) seeds then assessed for antiproliferative potential against human hepatocellular carcinoma cell line (HepG2). Further, HCC was induced in Wister albino rats by Diethylnitrosamine (DEN) ip injection (200 mg/kg bw), and CCl4 orally (2 ml/kg bw) for two months then subjected to GMann orally treatment (2 mg/kg bw) for one month. In results, isolated GMann is constituted of sugars (89.99 ± 2.3%), moisture (6.89 ± 0.45%), ash (0.06 ± 0.2%), and protein (2.81%) and composed mainly of mannose and galactose in ratio M/G 3.79. In vitro study, data revealed a concentration-dependent potency of GMann to induce cell death of HepG2 cells with IC50 value of 0.375 µg/ml. Mechanistic studies revealed the potential of GMann to arrest cell cycle at G2/M phase with induction of apoptosis. Biochemical results in vivo showed a significant reduction in serum transaminases (ALT and AST) as well as hepatic malondialdehyde (MDA) and nitric oxide (NOx). Molecular analysis declared a significant down-regulation in mRNA gene expression of both nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF-α). Furthermore, a significant down-regulation in the cellular oncogene-fos (C-fos) and marked up-regulation in Glycogen synthase kinase-3 (GSK-3ß) level were observed. These results were supported with histopathological investigation. Whereas GMann improved inflammatory and apoptotic markers, it could be a promising new therapeutic agent for HCC suppression and this warrant further development as a possible drug candidate for HCC.
Asunto(s)
Apoptosis/efectos de los fármacos , Caesalpinia/química , Carcinoma Hepatocelular/patología , Inflamación/patología , Neoplasias Hepáticas/patología , Hígado/efectos de los fármacos , Mananos/farmacología , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Galactosa/análogos & derivados , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/metabolismo , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Masculino , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Células Tumorales CultivadasRESUMEN
Nanotechnology is a promising era of medicine for developing targeted drug delivery system. Chitosan nanoparticles (CNPs) have attracted increasing attention for their wide applications as anticancer drugs. This article is concerned with the therapeutic index of chitosan nanoparticles against diethyl nitrosamine (DEN) induced hepatocellular carcinoma (HCC). HCC was induced in rats via repeated DEN administration in a dose of 200â¯mg/kg BW IP, 2 weeks later rats received (2â¯ml/kg BW) CCl4 orally for 2 months followed by daily treatment with chitosan nanoparticles in an oral dose of 12â¯mg/kg for 1 month. Then the gene expression of glycogen synthase kinase-3 (GSK-3), (c-FOS), nuclear factor kappa-B (NFκB) and tumor necrosis factor- α (TNF-α) were reported in rats sera and the correlation between GSK-3, C-Fos, NFÆB and TNF-α and liver tumorigenesis was investigated. The results elucidated that DEN significantly increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Marked increments in serum malondialdehyde (MDA) and nitric oxide (NOx) levels along with a slight reduction of glutathione (GSH) level were evidenced in HCC. Liver injury triggered an inflammatory response by enhancing the mRNA gene expression of NFκB and TNF-α. DEN effectively activated apoptotic markers GSK-3 and c-FOS. Oral administration of CNPs alleviated the oxidative, inflammatory and apoptotic hazards induced via DEN. The histopathological examination reinforced these results. The present study highlights the anti-inflammatory and anti-apoptotic potentials of CNPs against DEN-induced HCC.
RESUMEN
Obesity is one of the independent risk factors for several health problems, leading to metabolic perturbations and for which analytical approaches i.e., "metabolomics" is needed to monitor the underlying metabolic changes. In this study, obesity associated changes were assessed via serum metabolites analysis of obese rats fed on high fat diet. Obese rats were subsequently treated with different functional foods used for obesity management including pomegranate, grapefruit, and red cabbage in parallel to swimming exercise. Serum samples were analyzed using gas chromatography-mass spectrometry (GC-MS) followed by multivariate data analysis to classify samples and determine if such treatments can help revert obesity related metabolic changes back to normal status. Results led to the identification of several novel metabolites biomarkers for obesity related to lipids, amino acids and central tricarboxylic acid (TCA) pathways. Distinct variations in metabolite levels were recorded in obese rats compared to normal ones including l-aspartic, l-alanine, l-glutamine, l-glycine, phenylethanolamine, α-aminobutyric acid and ß-hydroxybutyric acid. Metabolomics approach developed herein provides novel insight onto the metabolic disturbances associated with obesity, which will assist in future drug design that can help mitigate against such changes.
Asunto(s)
Alimentos Funcionales , Aminobutiratos , Animales , Dieta Alta en Grasa , Cromatografía de Gases y Espectrometría de Masas , Metabolómica , Obesidad , RatasRESUMEN
The fabrication of hydroxyapatite-Co-ferrite nanocomposite coatings was performed on stainless steel by chronoamperometry technique. HA-CoFe2O4 nanocomposite films were characterized using X-ray diffraction, scanning electron microscopy, and vibrating sample magnetometer (VSM). The results reveal that CoFe2O4 nanoparticles dispersed within the HA matrix have flake and strip shapes. The magnetic property of the nanocomposite was increased by increasing the concentration of CoFe2O4 and a good saturation magnetization value was found to be 20.6emu/g with 50% CoFe2O4. By comparing with pure CoFe2O4, the composite still retain moderate magnetization as well as its biocompatible characters. The specific absorption rate (SAR) values were altered according to the change in CoFe2O4 concentration and the maximum SAR value was 125W/g. The incorporation of CoFe2O4 nanoparticles with HA coating was increased the corrosion resistance of HA in simulated body fluid (SBF). The results indicated that HA-CoFe2O4 nanocomposite coating could be a promising surface treatment technique for stainless steel medical implants as well hyperthermia treatment of cancer.
Asunto(s)
Nanocompuestos , Materiales Biocompatibles Revestidos , Cobalto , Durapatita , Técnicas Electroquímicas , Compuestos Férricos , Humanos , NeoplasiasRESUMEN
BACKGROUND: Recently, several research studies have been focused on the isolation and function of the polysaccharides derived from different algal species, which revealed multiple biological activities such as antioxidant and antitumor activities. This study assesses the possible breast cancer chemopreventive properties of common seaweeds, sea lettuce, Ulva lactuca (ulvan) polysaccharides using in vitro bioassays on human breast cancer cell line (MCF-7) and an in vivo animal model of breast carcinogenesis. METHODS: Cytotoxic effect of ulvan polysaccharides on MCF-7 was tested in vitro. For an in vivo investigation, a single dose of 25 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA) and ulvan polysaccharides (50 mg/kg body weight every other day) for 10 weeks were administered orally to the Wistar rats. RESULTS: Deleterious histopathological alterations in breast tissues including papillary cyst adenoma and hyperplasia of ductal epithelial lining with intraluminal necrotic materials and calcifications were observed in the DMBA-administered group. These lesions were prevented in the DMBA-administered group treated with ulvan polysaccharides. The immunohistochemical sections depicted that the treatment of DMBA-administered rats with ulvan polysaccharides markedly increased the lowered pro-apoptotic protein, p53, and decreased the elevated anti-apoptotic marker, bcl2, expression in the breast tissue. The elevated lipid peroxidation and the suppressed antioxidant enzyme activities in DMBA-administered control were significantly prevented by the treatment with ulvan polysaccharides. The elevated levels of inflammatory cytokines tumor necrosis factor-α and nitric oxide were significantly ameliorated in DMBA-administered rats treated with ulvan polysaccharides as compared to DMBA-administered control. CONCLUSION: In conclusion, ulvan polysaccharides at the level of initiation and promotion might have potential chemopreventive effects against breast carcinogenesis. These preventive effects may be mediated through the augmentation of apoptosis, suppression of oxidative stress and inflammation, and enhancement of antioxidant defense system.
RESUMEN
OBJECTIVE: To determine the metabolic response associate with dengue infection based on human gender metabolic differences by means of (1)H NMR-spectrometry. METHODS: The mid-stream urine collected from both male and female patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were analyzed with (1)H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were further selected and identified using Human Metabolome Database, Chenomx Profiler. RESULTS: The results pointed out that NMR urine profiling was able to capture human gender metabolic differences that are important for the distinction of classes of individuals of similar physiological conditions; infected with dengue. Distinct differences between dengue infected patients versus healthy individuals and subtle differences in male versus female infected with dengue were found to be related to the metabolism of amino acid and tricarboxylic acid intermediates cycle. CONCLUSIONS: The (1)H NMR metabolomic investigation combined with appropriate algorithms and pattern recognition procedures, gave an evidence for the existence of distinct metabolic differentiation of individuals, according to their gender, modulates with the infection risk.