30 research outputs found

    The effects of prenatal and neonatal exposure to electromagnetic fields on infant rat myocardium

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    Introduction: Electromagnetic fields (EMF) have adverse effects as a result of widespread use of electromagnetic energy on biological systems. The aim of this study was to investigate the effects of prenatal exposure to EMF on rat myocardium by biochemical and histopathological evaluations

    Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway.

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    peer reviewedInflammation is a crucial component of various stress-induced responses that contributes to the pathogenesis of major depressive disorder (MDD). Depressive-like behavior (DLB) is characterized by decreased mobility and depressive behavior that occurs in systemic infection induced by Lipopolysaccharide (LPS) in experimental animals and is considered as a model of exacerbation of MDD. We assessed the effects of melatonin on behavioral changes and inflammatory cytokine expression in hippocampus of mice in LPS-induced DLB, as well as its effects on NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation, oxidative stress and pyroptotic cell death in murine microglia in vitro. Intraperitoneal 5 mg/kg dose of LPS was used to mimic depressive-like behaviors and melatonin was given at a dose of 500 mg/kg for 4 times with 6 h intervals, starting at 2 h before LPS administration. Behavioral assessment was carried out at 24 h post-LPS injection by tail suspension and forced swimming tests. Additionally, hippocampal cytokine and NLRP3 protein levels were estimated. Melatonin increased mobility time of LPS-induced DLB mice and suppressed NLRP3 expression and interleukin-1β (IL-1β) cleavage in the hippocampus. Immunofluorescence staining of hippocampal tissue showed that NLRP3 is mainly expressed in ionized calcium-binding adapter molecule 1 (Iba1) -positive microglia. Our results show that melatonin prevents LPS and Adenosine triphosphate (ATP) induced NLRP3 inflammasome activation in murine microglia in vitro, evidenced by inhibition of NLRP3 expression, Apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, caspase-1 cleavage and interleukin-1β (IL-1β) maturation and secretion. Additionally, melatonin inhibits pyroptosis, production of mitochondrial and cytosolic reactive oxygen species (ROS) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. The beneficial effects of melatonin on NLRP3 inflammasome activation were associated with nuclear factor erythroid 2-related factor 2 (Nrf2) and Silent information regulator 2 homolog 1 (SIRT1) activation, which were reversed by Nrf2 siRNA and SIRT1 inhibitor treatment

    Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

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    Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner

    Ex-vivo Model Experimental and Simulation Results Suggesting Effective and Superficial Mucosal Photothermal Ablation at 1505 nm

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    Uncontrolled therapy depth of treatment strategies for mucosal lesions may lead to adverse side effects. Laser ablation therapy using near-infrared laser irradiation provides confined therapy depth limited with a thickness of mucosa

    Imaging of Isolated Exosomes by Correlative Microscopy

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    Correlative microscopy is a sophisticated imaging technique that combines optical and electron microscopes, with the most common approach being the integration of light microscopy and electron microscopy, known as correlative light and electron microscopy (CLEM). While CLEM provides a comprehensive view of biological samples, it presents a significant challenge in sample preparation due to the distinct processes involved in each technique. Striking a balance between these methods is crucial. Despite numerous approaches, achieving seamless imaging with CLEM remains a complex task. Exosomes, nanovesicles ranging from 30 to 150 nm in size, are enclosed by a lipid bilayer and released by various cell types. Visualizing exosomes poses difficulties due to their small size and minimal electric charge. However, imaging exosomes at high resolution offers a direct method to understand their morphology and functions. In this study, we evaluated exosome imaging with CLEM using a combination of confocal, transmission electron microscope, and scanning electron microscope (SEM). In addition, we conducted a comparative analysis of these two techniques, evaluating their suitability and efficiency in imaging nanoscale structures. In this study, we found that confocal-SEM correlation is more applicable for imaging exosomes. Moreover, we observed that exosomes were found in clusters in confocal-SEM correlation

    The Protective Effects of Fucoidan on Cisplatin Induced Testicular Cytotoxicity in Rats

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    Cisplatin is prevalently used as a chemotherapeutic agent for testis cancer, ovarian cancer, bladder cancer, brain tumors and many cancers such as those. Infertility and sterility may emerge, after treatment with chemotherapeutic agents, depending on patient characteristics and the dose of chemotherapeutic agent. Fucoidan is a sulfated polysaccharide, which is derived from brown seaweeds. It is first isolated in 1913 from marine brown algae by Henrik Kylin. Fucoidan is especially found in the cell-wall of marine brown algae. Many effects of fucoidan such as anti-inflammatory, anti-viral, anti-complement, anti-cancer, anti-oxidant and anti-coagulant effects have been revealed by many studies in the literature. Furthermore, some studies suggest that fucoidan may enhance the antineoplastic effects of anticancer drugs. Besides beneficial effects of fucoidan, no toxic or adverse effect has been shown to date. In this study, we aimed to investigate the effects of fucoidan on testicular tissue and its effects on cisplatin induced testicular damage when used concomitantly with cisplatin

    Guide mapping for effective superficial photothermal coagulation of the esophagus using computer simulations with ex vivo sheep model validation study

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    Objectives The transfer and widespread acceptance of laser-induced thermal therapy into gastroenterology remain a topic of interest. However, a practical approach to the quantitative effect of photothermal injury in the esophagus needs further investigation. Here, we aim to perform computer simulations that simulate laser scanning and calculate the laser-induced thermal damage area. The simulation engine offers the results in a guide map for laser coagulation with a well-confined therapeutic area according to laser irradiance and surface scanning speed. The study also presents validation experiments that include histology analyses in an ex vivo sheep esophagus model. Methods The simulation engine was developed based on the Monte-Carlo method and the Arrhenius damage integral. The computational model mimicked laser scanning by shifting the position of the calculated heat source in the grating system along the axis to be scanned. The performance of the simulations was tested in an ex vivo sheep esophagus model at a laser wavelength of 1505 nm. Histological analysis, hematoxylin-eosin staining, light microscope imaging, and block-face scanning electron microscopy were used to assess thermal damage to the tissue model. Results The developed simulation engine estimated the photothermal coagulation area for a surface scanning speed range of 0.5-8 mm/second and laser power of up to 0.5 W at a 0.9-nm laser diameter in a tissue model with a volume of 4 x 4 x 4 mm(3). For example, the optimum laser irradiation for effective photothermal coagulation in the mucosa and superficial submucosa depths was estimated to be between 16.4 and 31.8 W/cm(2), 23.2 and 38.1 W/cm(2) at 0.5 and 1 mm/second, respectively. The computational results, summarized as a guide map, were directly compared with the results of ex vivo tissue experiments. In addition, it was pointed out that the comparative theoretical and experimental data overlap significantly in terms of energy density. Conclusions Our results suggest that the developed simulation approach could be a seed algorithm for further preclinical and clinical trials and a complementary tool to the laser-induced photothermal coagulation technique for superficial treatments in the gastrointestinal tract. In future preclinical studies, it is thought that the simulation engine can be enriched by combining it with an in vivo model for different laser wavelengths

    Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model

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    Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42 degrees C with acute nerve damage observed above 46 degrees C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation

    Comparison of the acute effects of hemostatic agents on neural tissues in spine surgery: Histologic analysis in rat models

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    Objective: The most frightening and likely complication of chemical hemostatic agents is neurologic deficit. The histological basis of this potential complication is still unknown. The aim of this study is to observe the acute histologic effects of routinely used hemostatic agents on neural tissues in a rat model. Methods: Eighteen Winstar Albino rats were operated and same-level laminectomies were performed. The rats were divided into three groups. In group 1 (control group), surgical layers were sutured in routine manner after laminectomy. In group 2 (gelatin sponge group), dura mater was covered with gelatin sponge after laminectomy, while oxidized cellulose was used for coverage in group 3 (oxidized cellulose group). Neurologic evaluations were made for all test subjects. Fortyeight hours after the operation, rats were sacrificed and lumber spines were excised with all surrounding tissues for evaluation by light microscopy of the acute effects of agents on neural tissues. Neurologic scores and histologic findings were compared with double-blind evaluation. Results: There were no statistically significant differences between the three groups in the histologic findings and clinical evaluations. However, the inflammatory reaction was more severe in the oxidized cellulose group. Conclusion: Both gelatin sponge and oxidized cellulose did not increase the cellular necrosis of neural tissues. However, oxidized cellulose may lead to an increased local inflammatory reaction. [Arch Clin Exp Surg 2016; 5(1.000): 21-26

    The effects of prenatal and postnatal exposure to electromagnetic field on rat ovarian tissue

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    Exposure to an electromagnetic field (EMF) can have adverse effects on many organs and tissues, including the reproductive system. This study aimed to investigate the effects of EMF exposure during prenatal and postnatal periods on ovarian development in rat offspring. In this study, rat pups born from eight pregnant rats were used. EMF exposure was initiated on the first day of pregnancy and continued until the 42nd postnatal day. The blood and ovarian tissue samples of female offspring in sham and EMF groups were collected when they reached the age of 42 days. Follicle-stimulating hormone levels were significantly higher in the EMF group than in the sham group. Estradiol levels were significantly lower in the EMF group than in the sham group. Tissue-inducible nitric oxide synthase (iNOS) levels and expression were significantly greater in the EMF group than in the sham group. In the EMF group, congestion, bleeding areas, and degeneration of follicle structures were observed in ovarian tissue. The findings suggest that exposure to 50-Hz, 3-mT EMF used in this study during prenatal and postnatal periods may lead to impaired ovarian structure and function in female offspring. EMF may affect ovarian physiology by increasing iNOS levels and may lead to fertility disorders
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