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Water pollution represents one of the most important problems affecting the health of living organisms, so it was necessary to work on the formation of active materials to get rid of pollutants. In this study, Titanium dioxide (TiO2) doping Zinc oxide (ZnO) nanocomposites were produced via simple sonication method at 500 Hz in ethanol medium. At different weight concentrations (2.5, 5, 7.5, and 10 %). The morphology, structure configuration, chemical bonding, crystalline phase, and surface properties of obtained nanocomposites were characterized via FESEM, BET, XRD, XPS, RAMAN and FTIR instrumentation. The nanocomposites were employed as an adsorbent to eliminate the methyl orange (MO) and Indigo Carmine (IC) dyes from an aqueous solution. Batch removal experiments revealed that the elimination of MO and IC dyes by the TiZnO surface was pH and doping Ti concentration-dependent, with maximum removal occurring at pH = 7 for MO and pH = 3 for IC contaminants at 10 % doping Ti concentration (Ti (10 %)@ZnO). Langmuir model fit the absorptive removal of MO and IC dyes into the Ti (10 %)@ZnO surface well. The maximal removal capacity of Ti (10 %)@ZnO nanocomposite was found to be 994.24 mg. g-1 for MO and 305.39 mg. g-1 for IC. The Ti (10 %)@ZnO nanocomposite showed remarkable high stability towards the removal of both dyes through consecutive four cycles.
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In consideration of the chromones' therapeutic potential and anticancer activity, a new series of chromanone derivatives have been synthesized through a straightforward reaction between 6-formyl-7-hydroxy-5-methoxy-2-methylchromone (2) and various organic active compounds. The cytotoxic activity of the newly synthesized congeners was investigated against MCF-7 (human breast cancer), HCT-116 (colon cancer), HepG2 (liver cancer), and normal skin fibroblast cells (BJ1). The obtained data indicated that compounds 14b, 17, and 19 induce cytotoxic activity in the breast MCF7, while compounds 6a, 6b, 11 and 14c showed highly potent activity in the colon cancer cell lines. Overall, the results demonstrate that the potential cytotoxic effects of the studied compounds may be based on their ability to induce DNA fragmentation in cancer cell lines, down-regulate the expression level of CDK4 as well as the anti-apoptotic gene Bcl-2 and up-regulate the expression of the pro-apoptotic genes P53 and Bax. Furthermore, compounds 14b and 14c showed a dual mechanism of action by inducing apoptosis and cell cycle arrest. The docking studies showed that the binding affinity of the most active cytotoxic compounds within the active pocket of the CDK4 enzyme is stronger due to hydrophobic and H-bonding interactions. These results were found to be consistent with the experimental results.
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Antineoplásicos , Apoptosis , Cromonas , Simulación del Acoplamiento Molecular , Humanos , Cromonas/química , Cromonas/farmacología , Cromonas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Células MCF-7 , Línea Celular Tumoral , Células HCT116 , Células Hep G2 , Quinasa 4 Dependiente de la Ciclina/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Obesity has reached an epidemic proportion in the last thirty years, and it is recognized as a major health issue in modern society now with the possibility of serious social and economic consequences. By the year 2030, nearly 60% of the global population may be obese or overweight, which emphasizes a need for novel obesity treatments. Various traditional approaches, such as pharmacotherapy and bariatric surgery, have been utilized in clinical settings to treat obesity. However, these methods frequently show the possibility of side effects while remaining ineffective. There is, therefore, an urgent need for alternative obesity treatments with improved efficacy and specificity. Polymeric materials and chemical strategies are employed in emerging drug delivery systems (DDSs) to enhance therapy effectiveness and specificity by stabilizing and controlling the release of active molecules such as natural ingredients. Designing DDSs is currently a top priority research objective with an eye towards creating obesity treatment approaches. In reality, the most recent trends in the literature demonstrate that there are not enough in-depth reviews that emphasize the current knowledge based on the creation and design of DDSs for obesity treatment. It is also observed in the existing literature that a complex interplay of different physical and chemical parameters must be considered carefully to determine the effectiveness of the DDSs, including microneedles, for obesity treatment. Additionally, it is observed that these properties depend on how the DDS is synthesized. Although many studies are at the animal-study stage, the use of more advanced DDS techniques would significantly enhance the development of safe and efficient treatment approaches for obese people in the future. Considering these, this review provides an overview of the current anti-obesity treatment approaches as well as the conventional anti-obesity therapeutics. The article aims to conduct an in-depth discussion on the current trends in obesity treatment approaches. Filling in this knowledge gap will lead to a greater understanding of the safest ways to manage obesity.
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Nanotechnology has proven advantageous in numerous scientific applications, one being to enhance the delivery of chemotherapeutic agents. This present study aims to evaluate the mechanisms underlying the chemopreventive action of naringin-dextrin nanocomposites (Nar-Dx-NCs) against diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced lung carcinogenesis in male Wistar rats. DEN was administered intraperitoneally (i.p.) (150 mg/kg/week) for two weeks, followed by the oral administration of 2AAF (20 mg/kg) four times a week for three weeks. Rats receiving DEN/2AAF were concurrently treated with naringin or Nar-Dx-NCs orally at a dose of 10 mg/kg every other day for 24 weeks. Naringin and Nar-Dx-NCs treatments prevented the formation of tumorigenic cells within the alveoli of rats exposed to DEN/2AAF. These findings were associated with a significant decrease in lipid peroxidation, upregulation of antioxidant enzyme (glutathione peroxidase and superoxide dismutase) activity, and enhanced glutathione and nuclear factor erythroid 2-related factor 2 expression in the lungs. Naringin and Nar-Dx-NCs exerted anti-inflammatory actions manifested by a decrease in lung protein expression of tumor necrosis factor-α and interleukin-1ß and mRNA expression of interleukin-6, interferon-γ, nuclear factor-κB, and inducible nitric oxide synthase, with a concurrent increase in interleukin-10 expression. The anti-inflammatory effect of Nar-Dx-NCs was more potent than naringin. Regarding the effect on apoptosis, both naringin and Nar-Dx-NCs significantly reduced Bcl-2 and increased Bax and P53 expressions. Moreover, naringin or Nar-Dx-NCs induced a significant decrease in the expression of the proliferator marker, Ki-67, and the effect of Nar-Dx-NCs was more marked. In conclusion, Nar-Dx-NCs improved naringin's preventive action against DEN/2AAF-induced lung cancer and exerted anticarcinogenic effects by suppressing oxidative stress and inflammation and improving apoptotic signal induction and propagation.
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Calcium silicate cements have been greatly developed in the last decades through different approaches. Among these approaches, the inclusion of antibacterial agents or addition of metal oxides. Herein, calcium silicate cement containing fluorine (CFS) was developed from sodium fluorosilicate precursor for the first time using chemical perception method. Afterwards, metal oxide Bi2O3 or MgO or ZrO2 was individually mixed with CFS powder and blended together using Polycaprolactone polymer (PCL). The cement mixtures were characterized using DSC, XRD, FTIR and SEM/EDX to determine the effect of metal oxide on the pure CFS. Furthermore, mechanical, antibacterial and cell viability properties were evaluated for the developed CFS mixture cements. Moreover, these CFS mixture cements were implanted in male Wistar rats to determine the effect of metal oxides on the rate of bone reformation. The findings of physicochemical and morphological characterization showed no remarkable effects on the pure CFS after mixing with each metal oxide. However, enhanced compressive strengths (up to 104.07N/cm2), antibacterial activity and cell viability (up to 96%) were achieved for the CFS cement mixtures. Finally, the in vivo studies confirmed the biocompatibility of the CFS cement mixtures and especially those mixed with Bi2O3 or ZrO2. Therefore, this study supports that CFS blends with Bi2O3 or ZrO2 can be novel promising cementing materials for bone restoration.
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Cementos para Huesos , Calcio , Masculino , Ratas , Animales , Ratas Wistar , Cementos para Huesos/farmacología , Antibacterianos/farmacología , Cementos de Ionómero Vítreo , Óxidos/farmacologíaRESUMEN
The current study involves the design and synthesis of a newly synthesized pyrrolo[2,3-d]pyrimidine derivatives to contain chlorine atoms in positions 4 and 6 and trichloromethyl group in position 2 using microwave technique as a new and robust approach for preparation of this type of pyrrolo[2,3-d]pyrimidine derivatives. The chemical structure of the synthesized pyrrolo[2,3-d]pyrimidine derivatives 3-19 was well-characterized using spectral and elemental analyses as well as single-crystal X-ray diffraction. All compounds were tested in vitro against seven selected human cancer cell lines, namely, MCF7, A549, HCT116, PC3, HePG2, PACA2 and BJ1 using MTT assay. It was found that compounds 14a, 16b and 18b were the most active toward MCF7 with IC50 (1.7, 5.7, and 3.4 µg/ml, respectively) relative to doxorubicin (Dox.) (26.1 µg/ml). Additionally, compound 17 exerted promising cytotoxic effects against HePG2 and PACA2 with IC50 (8.7 and 6.4 µg/ml, respectively) relative to Dox. (21.6 and 28.3 µg/ml, respectively). The molecular docking study confirmed our ELISA result which showed the promising binding affinities of compounds 14a and 17 against Bcl2 anti-apoptotic protein. At the gene expression level, P53, BAX, DR4 and DR5 were up-regulated, while Bcl2, Il-8, and CDK4 were down-regulated in 14a, 14b and 18b treated MCF7 cells. At the protein level, compound 14b increased the activity of Caspase 8 and BAX (18.263 and 14.25 pg/ml) relative to Dox. (3.99 and 4.92 pg/ml, respectively), while the activity of Bcl2 was greatly decreased in 14a treated MCF7 (2.4 pg/ml) compared with Dox. (14.37 pg/ml). Compounds 14a and 14b caused cell cycle arrest at the G1/S phase in MCF7. Compounds 16b and 18b induced the apoptotic death of MCF7 cells. In addition, the percentage of fragmented DNA was increased significantly in 14a treated MCF7 cells.
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Alzheimer's disease (AD) is the most common cause of age-related neurodegeneration and cognitive decline. AD more commonly occurs in females than in males, so it is necessary to consider new treatments specifically targeting this population. The present study investigated the protective effects of Begacestat (γ-secretase inhibitor-953, GSI-953) and bone marrow-derived mesenchymal stem cells (BM-MSCs) during pregnancy on cognitive impairment in rat dams and neurodegeneration in offspring caused by the intracerebroventricular injection of Aß 25-35 before pregnancy. The performances of dams injected with amyloid-ß 25-35 (Aß 25-35) during behavioral tests were significantly impaired. The offspring of Aß 25-35-injected dams treated with BM-MSCs or GSI-953 showed a dramatically reduced number and size of activated microglial cells, enhancement in the processes length, and a decrease in the proinflammatory cytokine levels. Additionally, BM-MSC or GSI-953 therapy reduced Aß 25-35-induced increases in tau phosphorylation and amyloid precursor protein levels in the neonates' hippocampus and elevated the lower levels of glycogen synthase kinase-3 and brain-derived neurotrophic factor; moreover, reversed Aß 25-35-induced alterations in gene expression in the neonatal hippocampus. Finally, the treatments with BM-MSC or GSI-953 are globally beneficial against Aß 25-35-induced brain alterations, particularly by suppressing neural inflammation, inhibiting microglial cell activation, restoring developmental plasticity, and increasing neurotrophic signaling.
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This study was designed to assess the ameliorative effects of eugenol and to propose the possible mechanisms of action of eugenol in diethylnitrosamine (DENA)/acetylaminofluorene (AAF)-caused lung cancer in Wistar rats. To induce lung cancer, DENA at a dose of 150 mg/kg body weight (b.wt) for 2 weeks were intraperitoneally injected once each week and AAF was administered orally at a dose of 20 mg/kg b.wt. four times each week for the next 3 weeks. DENA/AAF-administered rats were orally supplemented with eugenol at a dose of 20 mg/kg b.wt administered once a day until 17 weeks starting from the 1st week of DENA administration. Lung histological lesions, including sheets of tumor cells, micropapillary adenocarcinoma, and apoptotic cells, resulting from the DENA/AAF dosage, were ameliorated by eugenol treatment. However, a significant drop in the levels of LPO in the lungs and a remarkable rise in GSH content and GPx and SOD activities were observed in DENA/AAF-administered rats treated with eugenol compared with those in DENA/AAF-administered controls. Moreover, in DENA/AAF-administered rats, eugenol supplementation significantly reduced TNF-α and IL-1ß levels and mRNA expression levels of NF-κB, NF-κB p65, and MCP-1 but significantly elevated the level of Nrf2. Furthermore, the DENA/AAF-administered rats treated with eugenol exhibited a significant downregulation of Bcl-2 expression levels in addition to a significant upregulation in P53 and Bax expression levels. Otherwise, the administration of DENA/AAF elevated the protein expression level of Ki-67, and this elevation was reversed by eugenol treatment. In conclusion, eugenol has effective antioxidant, anti-inflammatory, proapoptotic, and antiproliferative properties against lung cancer.
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Anticarcinógenos , Neoplasias Hepáticas Experimentales , Neoplasias Pulmonares , Ratas , Animales , Ratas Wistar , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéutico , 2-Acetilaminofluoreno/efectos adversos , 2-Acetilaminofluoreno/metabolismo , Dietilnitrosamina/toxicidad , Dietilnitrosamina/metabolismo , Eugenol/efectos adversos , FN-kappa B/genética , FN-kappa B/metabolismo , Apoptosis , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Hígado/patología , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patologíaRESUMEN
Nanotechnology holds great promise for the development of treatments for deadly human diseases, such as hepatocellular carcinoma (HCC). In the current study, we compared the hepatoprotective effects of naringin-dextrin nanoparticles (NDNPs) against HCC in male Wistar rats with those of pure naringin and investigated the underlying cellular and molecular mechanisms. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN, 150 mg/kg body weight (b.w.) per week) for two weeks, followed by oral administration of 2-acetylaminofluorene (2AAF, 20 mg/kg b.w.) four times per week for three weeks. DEN/2AAF-administered rats were divided into three groups that respectively received 1% carboxymethyl cellulose (as vehicle), 10 mg/kg b.w. naringin, or 10 mg/kg b.w. NDNP every other day by oral gavage for 24 weeks. Both naringin and NDNP significantly attenuated the harmful effects of DEN on liver function. Both compounds also suppressed tumorigenesis as indicated by the reduced serum concentrations of liver tumor markers, and this antitumor effect was confirmed by histopathological evaluation. Additionally, naringin and NDNP prevented DEN-induced changes in hepatic oxidative stress and antioxidant activities. In addition, naringin and NDNP suppressed inflammation induced by DEN. Moreover, naringin and NDNP significantly reduced the hepatic expression of Bcl-2 and increased Bax, p53, and PDCD5 expressions. Naringin and NDNP also reduced expression of IQGAP1, IQGAP3, Ras signaling, and Ki-67 while increasing expression of IQGAP2. Notably, NDNP more effectively mitigated oxidative stress and inflammatory signaling than free naringin and demonstrated improved antitumor efficacy, suggesting that this nanoformulation improves bioavailability within nascent tumor sites.
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Background: Liver cancer is the deadliest malignancy among common tumors. It is the top cause of cancer-related deaths in Egypt, and it is characterized by increasing occurrence among the population. The objective of this study was to determine the outcome of pre-treatment of IQGAP1-shRNA on induced mouse hepatocellular carcinoma model and evaluate the potency of this IQGAP1-shRNA plasmid to recover hepatic cancer as a new tool of cancer therapy. Therefore, we will use RNA interference (RNAi) technology to silence IQGAP1 oncogene to completely recover the chemically induced models for hepatic cancer by designing short RNAi specific for IQGAP1 gene in HCC cells in vivo and construct new vectors suitable for this purpose. We assigned mice into three groups: the first negative control group (NC) was injected with saline, the second control group was injected with shRNA (shNC), the third positive control group was injected with diethylnitrosamine (DENAA), and the fourth group was treated with the IQGAP1-shRNA prior to its exposure to DENA. Results: Our results revealed that the treated group with IQGAP1-shRNA with DENA developed very few cases of hepatic cancer when compared with the positive control group. The positive control group exhibited significant increases in the liver function level as well as a decrease in serum albumin levels when compared to both the treated and the negative control groups. The altered levels of the serum α-fetoprotein as well as of the tumor necrosis factor-alpha, and interleukin-4 in DENA-treated mice were significantly ameliorated by IQGAP1-shRNA administration. Flow cytometer analyses have indicated that the silencing of IQGAP1 cannot significantly modulate DENA-induced apoptosis in the circulating blood cells. Moreover, the elevated mRNA expression levels of IQGAP1, IQGAP3, KRas, HRas, interleukin-8, nuclear factor kappa B, caspase-3, caspase-9 and Bcl-2, were significantly decreased by the IQGAP1-shRNA treatment. However, the IQGAP2, DR4, DR5, p53 and BAX genes were found to be significantly up-regulated post-therapy. In agreement with these findings, IQGAP1-shRNA was able to modulate the DENA-induced histological changes in the mice liver which were represented by severe necrosis and hydropic degenerative changes. Conclusion: Our study revealed that IQGAP1-shRNA was able to preserve hepatocyte integrity and the liver histological architecture through the regulation of the expression of IQGAPs, Ras, TRAILs and IL-8 receptors, as well as of pro-apoptotic and anti-apoptotic genes. Therefore, the silencing of IQGAP1 could be part of a promising therapeutic strategy against hepatic cancer.
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Cadmium sulfide (CdS) quantum dots (QDs) were homogeneously embedded into chitosan (CTS), denoted as CdS@CTS, via an in situ hydrothermal method. The intact structure of the synthesized materials was preserved using freeze-drying. The materials were characterized using X-ray diffraction (XRD), X-ray photoelectron spectroscopy, transmission electron microscopy, high-resolution TEM, scanning TEM, dispersive energy X-ray (EDX) for elemental analysis and mapping, Fourier transform infrared spectroscopy, nitrogen adsorption-desorption isotherms, thermogravimetric analysis, UV-vis spectroscopy, and diffuse reflectance spectroscopy (DRS). The synthesis procedure offered CdS QDs of 1-7 nm (average particle size of 3.2 nm). The functional groups of CTS modulate the in situ growth of CdS QDs and prevent the agglomeration of CdS QDs, offering homogenous distribution inside CTS. CdS@CTS QDs can also be used for naked-eye detection of heavy metals with high selectivity toward copper (Cu2+) ions. The mechanism of interactions between Cu2+ ions and CdS@CTS QDs were further studied.
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BACKGROUND: Colorectal carcinoma (CRC) represents life-threatening problems worldwide. IQ motif containing GTPase activating protein 1 (IQGAP1) is acting as oncogenesis regulators. RNAi is proposed as promising cancer therapeutics. OBJECTIVE: The objective of this work to explore the consequences of the IQGAP1 silence as a goal for treating CRC using the HCT166 cells as a model for human colon cancer. METHODS: RNAi technology was used to design a short specific sequence of RNA (shRNA) to silence the IQGAP1 oncogene. The impact of IQGAP1 silencing on IQGAPs, Ras, IL-8, and TRAIL was investigated. Furthermore, the effect of IQGAP1 silencing on cell viability, proliferation, apoptosis, and invasive capacity was investigated. RESULTS: The present results revealed that IQGAP1 shRNA-treated HCT166 cells showed no invasive capacity compared to the control cells. The silencing of IQGAP1 induced remarkable downregulation of IQGAP1, RAS (H&K), IL-8, CXCR1, CXCR2, NF-kB, BCL-2, and apoptosis of HCT166 cells. On the contrary, IQGAP2, IQGAP3, DR4, DR5, CASP-3, and BAX genes were significantly up-regulated. CONCLUSION: The IQGAP1 regulates the expression of IQGAPs, Ras, IL-8 receptors, and the apoptotic network. Therefore, the silence of IQGAP1 is a promising strategy for colon cancer therapy.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Colon/genética , Neoplasias del Colon/terapia , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Proteínas Activadoras de GTPasa , Humanos , Interleucina-8/genética , ARN Interferente Pequeño/genética , Proteínas Activadoras de ras GTPasa/genética , Proteínas Activadoras de ras GTPasa/metabolismoRESUMEN
Hybrid polymer films of polyvinyl pyrrolidone (PVP)/polyvinyl alcohol (PVA) embedded with gradient levels of Bi-powder were prepared using a conventional solution casting process. XRD, FTIR, and SEM techniques have been used to examine the micro/molecular structure and morphology of the synthesized flexible films. The intensities of the diffraction peaks and transmission spectrum of the PVP/PVA gradually declined with the introduction of Bi-metal. In addition, filler changes the microstructure surface of the pure film. The modification in the microstructure leads to an enhancement in the optical absorption characteristic of the blend films. The indirect allowed transition energy was calculated via Tauc's and ASF (Absorption Spectra Fitting) models. The decrease in the hybrid film's bandgap returns to the localized states in the forbidden region, which led the present films to be suitable for photo-electric, solar cell, etc., applications. The relation between the transition energy and the refractive index was studied. The enhancement in the refractive index with Bi-metal concentrations led to use the as-prepared films in optical sensors. The rise of Bi-metal concentrations leads also to the improvement of the nonlinear susceptibility and refractive parameters. The optical limiting characteristics revealed that the higher concentration dopant films reduce the light transmission intensity which is appropriate for laser attenuation and optical limiting in photonic devices. The results suggest that hybrid films are promising materials in a wide range of opto-electronic applications.
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Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.
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OBJECTIVE: We aimed to investigate the signalling crosstalk of TNF-related apoptosis-inducing ligand, TRAIL death receptors, tumour protein p53, and programmed cell death (PDCD5) with IQGAPs. Also, we targeted the crosstalk between IQGAPs genes with decoy receptors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and interleukins -8 (IL-8) and its receptor genes in a designed model of hepatocellular carcinoma induced in male Balb/c mice. METHODS: The presence of HCC was confirmed by histological and morphological alterations. In parallel to the incidence of hepatic cancer, we found lung, heart, and kidney cancer after treatment with DEN. RESULTS: Our results show that the expression of mRNA of IQGAP1, TRAIL decoy receptors, NF-κB, and IL-8 genes was elevated in hepatocellular carcinoma, as compared to normal liver tissue, while their expression was further up-regulated by increasing the dose of diethylnitrosamine. The expression of IQGAP2, TRAIL death receptors, p53, and PDCD5 was significantly down-regulated in HCC (pË0.05). For confirmation of gene expression, protein levels of both IQGAP1 and P53 were measured by western blot analysis, which showed that diethylnitrosamine enhanced protein expression of IQGAP1 and diminished that of p53. CONCLUSION: IQGAPs have a direct signaling relationship with p53, IL-8, and TRAIL family. This interaction is recognized as a key signalling pathway for hepatocellular carcinogenesis.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Activadoras de ras GTPasa/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Dietilnitrosamina/administración & dosificación , Modelos Animales de Enfermedad , Regulación hacia Abajo , Interleucina-8/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Transducción de Señal/genética , Regulación hacia ArribaRESUMEN
OBJECTIVE: Hypertensive pulmonary edema is a fatal condition unless early and properly diagnosed and managed. Central blood pressure (cBP) has been proven to be more associated with adverse cardiovascular events. We aimed to study the correlation between cBP and heart damage in patients with Hypertensive pulmonary edema. METHODS: We included 50 patients admitted to the emergency department in a university hospital for hypertensive pulmonary edema, 27 women and 23 men aged 50 to 70 years. We excluded patients with suspected acute coronary syndrome, significant valvular heart disease, and pericardial diseases. We measured cBP non-invasively from pulse wave analysis of the brachial artery. Brain natriuretic peptide (BNP) and cBP were repeatedly measured for every patient. RESULTS: The median BNP levels of patients significantly decreased from 284 pg/ml (232-352.5) to 31.5 pg/ml (24-54) on discharge, P < 0.001. We found a significant correlation between admission BNP and central SBP (cSBP), urea, creatinine, arterial blood gases parameters, and left ventricular end-diastolic diameter (LVEDD). Concurrently, BNP at discharge was correlated with age, central DBP (cDBP), urea, creatinine, LVEDD, partial oxygen pressure (pO2), and oxygen saturation (SO2). Delta BNP was correlated with cSBP, peripheral SBP, urea, creatinine, pO2, and SO2. Linear regression analysis revealed that creatinine, and cSBP, were independent predictors of admission BNP, while urea and cDBP were the independent predictors of discharge BNP. CONCLUSION: This simple, noninvasive method of cBP measurement was significantly associated with the extent of myocardial damage in patients presenting with hypertensive pulmonary edema.
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Hipertensión , Edema Pulmonar , Anciano , Presión Sanguínea , Determinación de la Presión Sanguínea , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico , Edema Pulmonar/complicaciones , Edema Pulmonar/diagnósticoRESUMEN
In the current investigation, mesoporous silica nanoparticles were obtained by various techniques, namely sol-gel (S1), micro-emulsion (S2) and hydrothermal synthesis (S3). The effect of those methods on the final features of the obtained mesoporous silica nanoparticles was studied. The obtained nanoparticles were investigated by TEM, BET surface area, Zetasizer, XRD and FTIR. The preparation method effect was evaluated on the drug release behaviour using doxycycline hyclate as a model drug. In addition, the degree of their compatibility against Saos-2 cell line was also determined. The morphology and microstructure of silica nanoparticles were found to be dependent on the utilised method. Those techniques produced particles with particle sizes of 50, 30-20 and 15 nm and also surface areas of 111.04, 164 and 538.72 m2 /g, respectively, for S1, S2 and S3. However, different preparation methods showed no remarkable changes for the physical and chemical integrities. The drug release test showed faster release from S2 compared with S1 and S3, which make them more applicable in cases require large doses for short periods. However, the release behaviour of S3 was satisfied for treatments which require long period with relatively highest release rate. The preparation method influenced the cell viability as S1 and S2 showed acceptable cell cytotoxicity compared with S3.
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Nanopartículas , Dióxido de Silicio , Liberación de Fármacos , Tamaño de la Partícula , PorosidadRESUMEN
BACKGROUND: The management of hypertensive disorders of pregnancy (HDP) during hospitalization requires an accurate blood pressure (BP) measurement, mainly by invasive intra-arterial reading. Nevertheless, little is known about the precision of non-invasive (NI) central BP measurements in HDP. We aimed to assess the accuracy of NI central BP assessment in comparison to invasive BP measurement in HDP. This cross-sectional study included all patients with HDP that were admitted to university hospitals for high BP control, from December 2018 till December 2019, and 10 healthy matched non-hypertensive controls. Patients were compared for demographic, anthropometric, and echocardiographic data. In all subjects, invasive BP assessment was done by radial arterial cannulation and NI assessment of BP was performed by an oscillometric automated device (Mobil-O-Graph); the comparison was done after initial control of BP. RESULTS: One hundred patients were included and divided into 3 groups (pre-existing hypertension (HTN), gestational HTN, and pre-eclampsia). There was no statistically significant difference between NI central and invasive methods in measuring both systolic BP (SBP) (126.39 ± 14.5 vs 127.43 ± 15.3, p = 0.5) and diastolic BP (82.41 ± 9.0 vs 83.78 ± 8.9, p = 0.14) among the total studied population. A strong positive correlation was found between NI central and invasive SBP (r = 0.96, p < 0.001). HDP was associated with an increase in arterial stiffness, left ventricular diastolic dysfunction, and complications. CONCLUSION: Non-invasive measurement of BP using oscillometric automated devices is as accurate as the invasive method, and it is a practical safe method in pregnant women with hypertensive disorders (CTR no. = NCT04303871).
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INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disorder commonly attributed to fatty acid deposition that can induce hepatic necroinflammation, defined as nonalcoholic steatohepatitis (NASH). It is strongly associated with obesity. Laparoscopic sleeve gastrectomy (LSG) is a favorable surgical modality for the treatment of morbid obesity. AIM: Our study evaluated the impact of LSG on patients with NAFLD and morbid obesity, 3 months after the operation, through clinical and biochemical characteristics, clinico-biochemical indices, and imaging parameters. PATIENTS AND METHODS: Morbidly obese patients with NAFLD±NASH underwent LSG. They were thoroughly evaluated clinically (body weight, body mass index, waist circumference) and biochemically (transaminases and triglycerides), as well as through the fatty liver index (FLI), the hepatic steatosis index (HSI), and ultrasound elastography imaging studies (liver stiffness measurement [LSM] and the controlled attenuation parameter [CAP]), before and 3 months after the LSG. RESULTS: Twenty-six obese patients with NAFLD underwent LSG that resulted in a significantly high reduction in all the parameters analyzed, except for liver transaminases. CONCLUSION: LSG is considered an efficient surgical modality for the treatment of morbidly obese patients with NAFLD.
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This study aims to reduce embryonic mortality, increase body weight, and improve immune system in chicken. A total of 240 eggs were assigned to three treatments (n = 60) and injected with cooper (Cu), zinc (Zn), and iron (Fe) loaded by montmorillonite (Mnt), and one untreated group (n = 60). Some hormones and enzymes related with growth were measured in terms of serum, and expression of some genes related to growth, immune, and programmed cell deaths that were determined in the liver and spleen of chicken by RT-qPCR. The embryonic death on the fifth and seventh days after injecting eggs with Fe-Mnt was less obvious than in other groups. The heaviest body weight was recorded for Fe-Mnt and Cu-Mnt treatment. Fe-Mnt treatment had higher serum GSH, SOD, GH, and Myostatin contents and lower MDA than those in the other treatments. Cu-Mnt treatment included the highest contents of CAT enzyme and IGF-1 hormone in serum. The highest expression of IGF-1, GH, BCL6, and SYK genes in liver tissue were recorded by Zn-Mnt, IGFBP2, FGF8, and IFNW1 genes by Cu-Mnt, and TC1RG1 and IFNW1 genes by Fe-Mnt in spleen tissue. In conclusion, Fe-Mnt was the best treatment for reducing embryonic mortality, and increasing body weight of chickens and expression of growth and immune genes, followed by Cu-Mnt treatment.