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The aim of this study was to investigate the possible protective effects of apelin, which is known to have antioxidant and anti-inflammatory effects, on changes in neurogenesis in newborns of pregnant rats with L-NAME-induced preeclampsia. Wistar albino female rats were divided into four experimental groups: Control, Apelin, Preeclampsia and Preeclampsia + Apelin. Blood pressure was measured on the 5th, 11th and 17th days of gestation, urine protein was analyzed from urine samples collected for 24 h on the 6th, 12th and 18th days and serum creatinine was analyzed from serum samples. Maternal kidney and placenta tissues were obtained to establish the preeclampsia model, and neonatal brain tissues including the cortex, hippocampus and cerebellum regions were obtained to investigate neurogenesis and examined by histological and immunohistochemical methods. The number of newborns, body weight and brain weight of the newborns were measured. eNOS, IL-10, nNOS and NO levels in the brain analyzed via ELISA. Mean arterial pressure, urine protein and serum creatinine increased in the preeclampsia. Newborn weight decreased in the Preeclampsia group, the values in the Preeclampsia + Apelin group were closer to the Control and Apelin groups. In the Preeclampsia group, edema and dilatation in the proximal and distal tubules of kidneys, perivillous fibrin deposition and increase in syncytial nodules of placenta were observed. VEGF immunoreactivity decreased and iNOS immunoreactivity increased in both kidney and placenta. In neonatal brain tissue examinations, cytotoxic edema accompanied by thinning of cortex, delayed migration and lower cell counts in the hippocampus, and increase in intercellular spaces and EGL thickening in the cerebellum were observed in the preeclampsia. Expression of NeuN, GFAP, MBP, IL-10, eNOS, nNOS and NO levels decreased, whereas expression of Iba-1 increased in the preeclampsia. In the Preeclampsia + Apelin group, these findings were similar to the Control and Apelin groups. Apelin administration was found to be beneficial for preventing the adverse consequences of preeclampsia, but further experimental and clinical studies are needed to better understand these effects.
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Animais Recém-Nascidos , Apelina , Encéfalo , NG-Nitroarginina Metil Éster , Neurogênese , Pré-Eclâmpsia , Ratos Wistar , Feminino , Gravidez , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/metabolismo , Animais , Apelina/metabolismo , Neurogênese/efeitos dos fármacos , Ratos , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Placenta/metabolismo , Modelos Animais de Doenças , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Interleucina-10/metabolismo , Interleucina-10/sangue , Óxido Nítrico Sintase Tipo I/metabolismoRESUMO
The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder.
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Antioxidantes , Transtorno do Espectro Autista , Compostos Benzidrílicos , Glucosídeos , Fator de Crescimento Insulin-Like I , Fator 2 Relacionado a NF-E2 , Propionatos , Animais , Glucosídeos/farmacologia , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/induzido quimicamente , Fator de Crescimento Insulin-Like I/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Masculino , Compostos Benzidrílicos/farmacologia , Propionatos/farmacologia , Antioxidantes/farmacologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Modelos Animais de Doenças , Ratos Sprague-Dawley , Inibidores do Transportador 2 de Sódio-Glicose/farmacologiaRESUMO
Exposure to ionizing radiation leads to oxidative stress and neuroinflammation, resulting in neurocognitive impairments. Adverse effects are also associated with glutamate-induced excitotoxicity due to alterations in the composition of glutamate receptors. Ketamine, which is a noncompetitive NMDA glutamate receptor antagonist, has been stated to exert an impact on glutamatergic receptors. This study aims to reveal the possible alleviating or preventive effects of ketamine, which maintains glutamate homeostasis and decreases neurodegeneration, in a radiation-induced neurotoxicity model. Twenty-one female Wistar Queryrats were included in the study and 14 of these underwent whole brain irradiation (IR) with a 20 Gray single dose. Animals were allocated into three groups. Group 1: Normal control; Group 2: Placebo / IR + Saline; Group 3: IR + Ketamine. Ketamine was administered in addition to IR to rats in Group 3. The one-way ANOVA statistical test was used to compare groups. The value of p < 0.05 was considered statistically significant. When administered in addition to irradiation, ketamine treatment significantly increased scores in the three-chamber sociability test, open field test, and passive avoidance learning test. It also raised neuron counts in the hippocampal CA1 and CA3 regions as well as in Purkinje cells, and enhanced levels of brain-derived neurotrophic factor and tyrosine receptor kinase-B. Furthermore, ketamine administration resulted in decreased levels of glial fibrillary acidic protein, malondialdehyde, and tumor necrosis factor-alpha, indicating a reduction in neuroinflammation and oxidative stress. Ketamine exerted a significant protective impact on radiation-induced neurocognitive impairments and enhanced social-memory capacity by reducing neuronal loss, oxidative stress, and neuroinflammation. Our findings suggest that ketamine is beneficial in the treatment or prevention of neurodegeneration via the regulation of the BDNF/TrkB signaling pathway besides decreasing neuroinflammation and blocking NMDA receptors.
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Administração Intranasal , Encéfalo , Ketamina , Fármacos Neuroprotetores , Ratos Wistar , Animais , Ketamina/farmacologia , Feminino , Ratos , Fármacos Neuroprotetores/farmacologia , Encéfalo/efeitos da radiação , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiaçãoRESUMO
Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell aging is oxidative stress and it is known to have a role in idiopathic pulmonary fibrosis. In this paper, the protective effect of the E-CG-01 (3,4-lacto-cycloastragenol) molecule in terms of its antioxidant properties was evaluated in the bleomycin induced mice lung fibrosis model. Bleomycin sulfate was administered as a single dose (2.5â¯U/kg body weight) intratracheally to induce lung fibrosis. E-CG-01 was administered intraperitoneally in three different doses (2â¯mg/kg/day, 6â¯mg/kg/day, and 10â¯mg/kg/day) for 14 days, starting three days before the bleomycin administration. Fibrosis was examined by Hematoxylin-Eosin, Masson Trichrome, and immunohistochemical staining for TGF-beta1, Type I collagen Ki-67, and gama-H2AX markers. Activity analysis of catalase and Superoxide dismutase enzymes, measurement of total oxidant, total glutathione, and Malondialdehyde levels. In histological analysis, it was determined that all three different doses of the molecule provided a prophylactic effect against the progression of fibrosis compared to the bleomycin control group. However, it was observed that only the molecule applied in the high dose decreased the total oxidant stress level. Lung weight ratio increased in the BLM group but significantly reduced with high-dose E-CG-01. E-CG-01 at all doses reduced collagen deposition, TGF-ß expression, and Ki-67 expression compared to the BLM group. Intermediate and high doses of E-CG-01 also significantly reduced alveolar wall thickness and edema formation. These findings suggest that E-CG-01 has potential therapeutic effects in mitigating lung fibrosis through its antioxidant properties.
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Antioxidantes , Bleomicina , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Fibrose Pulmonar , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/prevenção & controle , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Masculino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Superóxido Dismutase/metabolismoRESUMO
INTRODUCTION: Chronic subdural hematoma (cSDH), a condition that develops over time, is characterized by inflammation, angiogenesis, and membrane development. As the population's average age increases, the incidence of cSDH is expected to grow. While surgery is the primary treatment technique, medicinal therapy options are being explored for high-risk patients. Currently, the most effective therapy combination is dexamethasone (Dex) and atorvastatin (Ato); however, it is associated with an increased risk of mortality. This study explored the effects of bevacizumab (Bev), a vascular endothelial growth factor antagonist, on cSDH. MATERIALS AND METHODS: Ninety-five rats were divided into four groups (n = 18): sham, control hematoma, Dex-Ato, and Bev. Two separate autologous blood injections into the subdural space were used as the model. Weight was monitored for all rats to assess changes in their overall health. The control group was given i.p. saline, the Dex-Ato treatment was given by gavage, and the Bev treatment was given i.p. On seventh, 14th and 21st days six rats from each group were sacrificed and analyzed, while 23 rats were excluded from the experiment. RESULTS: The maximum immunological response to cSDH was observed on day 14. Hematoma volume decreased over time in all groups. Dex-Ato and Bev were both found effective, while Dex-Ato caused weight loss. CONCLUSION: Bev had similar effects to the Dex-Ato group and was well tolerated by rats. Given that cSDH is a disease of the elderly and vulnerable populations, Bev may be a viable alternative that can shed light on the disease's etiology for future research.
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The neuroprotective effects of choline chloride, an essential nutrient, a precursor for the acetylcholine and synthesis of membrane phospholipids, have been associated with neurological and neurodegenerative diseases. Its contribution to autism spectrum disorder, a neurodevelopmental disorder, remains unknown. Thus, we aimed to evaluate the effects of choline chloride on social behaviours, and histopathological and biochemical changes in a rat autism model. The autism model was induced by administration of 100 µg/kg lipopolysaccharide (LPS) on the 10th day of gestation. Choline chloride treatment (100 mg/kg/day) was commenced on PN5 and maintained until PN50. Social deficits were assessed by three-chamber sociability, open field, and passive avoidance learning tests. Tumour necrosis factor alpha (TNF-α), interleukin-2 (IL) and IL-17, nerve growth factor (NGF), and glutamate decarboxylase 67 (GAD67) levels were measured to assess neuroinflammatory responses. In addition, the number of hippocampal and cerebellar neurons and glial fibrillary acidic protein (GFAP) expression were evaluated. Social novelty and passive avoidance learning tests revealed significant differences in choline chloride-treated male rats compared with saline-treated groups. TNF-α, IL-2, and IL-17 were significantly decreased after choline chloride treatment in both males and females. NGF and GAD67 levels were unchanged in females, while there were significant differences in males. Histologically, significant changes in terms of gliosis were detected in hippocampal CA1 and CA3 regions and cerebellum in choline chloride-treated groups. The presence of ameliorative effects of choline chloride treatment on social behaviour and neuroinflammation through neuroinflammatory, neurotrophic, and neurotransmission pathways in a sex-dependent rat model of LPS-induced autism was demonstrated.
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Transtorno Autístico , Colina , Modelos Animais de Doenças , Lipopolissacarídeos , Neurônios , Animais , Ratos , Masculino , Colina/farmacologia , Feminino , Lipopolissacarídeos/toxicidade , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/patologia , Transtorno Autístico/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurônios/metabolismo , Comportamento Social , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/patologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , Caracteres Sexuais , Gravidez , Ratos Wistar , Aprendizagem da Esquiva/efeitos dos fármacos , Deficiências da Aprendizagem/induzido quimicamente , Deficiências da Aprendizagem/patologiaRESUMO
The neurodegenerative mechanisms of Alzheimer's disease (AD) are not fully understood, but it is believed that amyloid beta (Aß) peptide causes oxidative stress, neuroinflammation, and disrupts metabotropic glutamate receptor 5 (mGluR5) signaling by interacting with cholesterol and caveolin-1 (Cav-1) in pathogenic lipid rafts. This study examined the effect of 2-hydroxypropyl-ß-cyclodextrin (HP-CD) on cholesterol, oxidative stress (total oxidant status), neuroinflammation (TNF-α), and mGluR5 signaling molecules such as PKCß1, PKCß2, ERK1/2, CREB, BDNF, and NGF in Aß (1-42)-induced neurotoxicity. The Sprague-Dawley rats were divided into four groups: control (saline), Aß (1-42), HP-CD (100 mg/kg), and Aß (1-42) + HP-CD (100 mg/kg). All groups received bilateral stereotaxic injections of Aß (1-42) or saline into the hippocampus. After surgery, HP-CD was administered intraperitoneally (ip) for 7 days. Cholesterol, TNF-α, and TOS levels were measured in synaptosomes isolated from hippocampus tissue using spectrophotometry, fluorometry, and enzyme immunoassay, respectively. The gene expressions of Cav-1, mGluR5, PKCß1, PKCß2, ERK1/2, CREB, BDNF, and NGF in hippocampus tissue were evaluated using reverse transcription PCR after real-time PCR analysis. Treatment with Aß (1-42) significantly elevated cholesterol, TOS, TNF-α, Cav-1, PKCß2, and ERK1/2 levels. Additionally, mGluR5, CREB, and BDNF levels were shown to be lowered. HP-CD reduced cholesterol, TOS, and TNF-α levels while increasing mGluR5, CREB, and BDNF in response to Aß (1-42) treatment. These findings indicate that HP-CD may have neuroprotective activity due to the decreased levels of cholesterol, oxidative stress, and neuroinflammation, as well as upregulated levels of mGluR5, CREB, and BDNF.
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PURPOSE: The aim of this study is to define the intramuscular nerve distribution of the sternocleidomastoid muscle (SCM) and the innervation zones (IZ) to describe the optimal botulinum toxin injection sites. METHODS: The cricoid cartilage (CC), laryngeal prominence (LP) and hyoid bone (HB) and angle of mandible (AM) were determined as landmarks. The length of the muscles were measured between the sternoclavicular joint and tip of the mastoid process. SCM was evaluated in two parts as anterior and posterior divided by the line where the length of the muscle was measured. Measurements were made to define the relationships of the SCM with common carotid artery, internal and external jugular veins. IZ were described according to these vessels. Afterwards, Modified Sihler's staining technique was applied to expose the intramuscular nerve distribution. RESULTS: The average length of SCM was 160,1 mm. Motor entry point of the accessory nerve fibers were between the AM-HB lines, in the range of 30-40% of the muscle length, and in the posterior part of the muscles. IZ were between the HB-CC lines in the anterior and posterior part. When this interval was examined according to the vessels, the optimal injection sites were between the LP-CC lines. CONCLUSIONS: This study shows the position of the intramuscular nerve fibers endings of the SCM according to the chosen landmarks and the relationship of the IZ with the vessels to prevent complications. These results can be used as a guide for safe and effective botulinum toxin injections with optimal quantities.
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Pontos de Referência Anatômicos , Músculos do Pescoço , Humanos , Injeções Intramusculares/métodos , Masculino , Músculos do Pescoço/inervação , Feminino , Cadáver , Toxinas Botulínicas/administração & dosagem , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Radiofrequency (RF)-based devices are frequently used in plastic surgeries. In the current literature, no comparative experimental study has demonstrated the histological and immunological effects of these devices that are frequently used in the facial area. In this study, we investigated the histological and immunological effects of Bipolar RF (BodyTite) and Microneedle RF (Morpheus 8) devices in the rat abdominal region. METHODS: 24 rats were used in this study. The rats were divided into four groups: group I: Control. In group II, BodyTite was applied to the abdominal region. Group III: Morpheus 8 was applied to the abdominal region. Group IV: Both Morpheus 8 and BodyTite were applied to the abdominal region. The histological and immunological features of the tissues in the groups were examined using light microscopy, and collagen formation and desmosome structures were examined using light microscopy. RESULTS: Collagens in Group II were thinner than those in the other groups. In addition, there were fewer vessels in Group III. The collagen scores were as follows: Group II:1.5; Group III:2; and Group IV:3. The VEGF scores were II:2.5, group III:2, and IV:3, respectively. The collagen score in group II and VEGF score in group III were significantly lower than those in the other groups. In addition, the bonds between desmosomes in group III were found to be looser using electron microscopy. Collagen morphology in groups III and IV was found to be similar to that in group I. CONCLUSIONS: The conclusion of comparison RF-based devices increased tissue regeneration and healing. CLINICAL RELEVANCE STATEMENT: The use of radiofrequency devices has increased in plastic surgery practice over the past two decades, particularly emerging as a unique alternative for non-surgical candidates. There is a lack of experimental studies concerning these commonly used devices in clinical practice.
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OBJECTIVE: The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high-dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus. MATERIALS AND METHODS: A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9-20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10 mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti-GFAP, and antisynaptophysin staining methods. RESULTS: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group. CONCLUSION: It is concluded that high-dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.
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Cafeína , Hipocampo , Melatonina , Fármacos Neuroprotetores , Ratos Wistar , Animais , Feminino , Melatonina/farmacologia , Melatonina/administração & dosagem , Hipocampo/efeitos dos fármacos , Gravidez , Cafeína/administração & dosagem , Cafeína/farmacologia , Ratos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Estimulantes do Sistema Nervoso Central/toxicidade , Estimulantes do Sistema Nervoso Central/administração & dosagem , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: Open reduction with internal fixation is the preferred treatment option for displaced facial bone fractures. The superior mechanical properties of metallic plates have made them the most widely used material in existing bone fixation systems. However, after the healing period, these permanent plates can cause various problems. Alternative bioresorbable materials are being investigated to reduce these potential problems. This study compares bone stability and viability by using graphene oxide (GO)-doped poly-lactic-co-glycolic acid (PLGA) nanofiber plates and titanium plates for rats with fractured mandibles. MATERIALS AND METHODS: The study included 20 male Sprague-Dawley rats, divided into four groups: a control group (Group I), a mandibular fracture group with no additional application (Group II), a mandibular fracture group repaired with titanium plates (Group III), and a mandibular fracture group repaired with GO-PLGA plates (Group IV). After 2 months, all of the rats were euthanized. A bone compression test was performed to assess bone stability, and a histological examination was performed to evaluate bone healing. RESULTS: The osteocyte lacunae, Haversian ducts, canaliculi, and vascular structures of Group IV were found to be higher. In the compression test, vertical compression was applied to the bone axis, and Group IV had a higher maximum load and maximum stretch. GO-PLGA plates were found to be statistically superior to titanium plates in terms of both bone stability and bone healing (p < 0.05). CONCLUSIONS: The present study found that GO-PLGA plates are more effective than titanium plates for the treatment of mandibular corpus fractures.
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Implantes Absorvíveis , Placas Ósseas , Fixação Interna de Fraturas , Grafite , Fraturas Mandibulares , Nanofibras , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos Sprague-Dawley , Titânio , Animais , Masculino , Ratos , Fraturas Mandibulares/cirurgia , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Consolidação da FraturaRESUMO
Microbial secondary metabolites, which play a pivotal role in struggling with infectious diseases, are the new source for controlling bacterial contaminations and possess a strong antimicrobial potential. The present study is designed to evaluate the in vitro and in vivo bactericidal activities of prodigiosin against Staphylococcus aureus. For this purpose, Serratia marcescens was used to produce prodigiosin. Characterization of the prodigiosin was carried out using NMR. In addition, bioautographic detection of prodigiosin was detected by TLC. Antibacterial assays, in vivo epicutaneous infection tests, swap analyses, and histopathological examinations were determined. The results revealed that prodigiosin was detected by NMR and TLC. According to antimicrobial susceptibility tests, prodigiosin is an efficient bactericidal compound that demonstrated strong antibacterial activity toward S. aureus. In vivo, animal studies determined that the strong inhibition of S. aureus-caused epidermal infection occurs by prodigiosin at 48 h. Histopathological results showed that S. aureus + prodigiosin skin sections consist of improved and healthy tissues without any infection area compared with the S. aureus and control groups. The in vivo study verified the antibacterial results with swap analyses, and histopathological findings showed that prodigiosin is a promising microbial metabolite effective against S. aureus infection. This study proved that prodigiosin with excellent bioactivity exhibited antibacterial properties, which might possess massive potential for new therapeutic approaches using micro-organisms.
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Recent research on placental, embryo, and brain organoids suggests that the COVID-19 virus may potentially affect embryonic organs, including the brain. Given the established link between SARS-CoV-2 spike protein and neuroinflammation, we sought to investigate the effects of exposure to this protein during pregnancy. We divided pregnant rats into three groups: Group 1 received a 1 ml/kg saline solution, Group 2 received 150 µg/kg adjuvant aluminum hydroxide (AAH), and Group 3 received 40 µg/kg spike protein + 150 µg/kg AAH at 10 and 14 days of gestation. On postnatal day 21 (P21), we randomly separated 60 littermates (10 male-female) into control, AAH-exposed, and spike protein-exposed groups. At P50, we conducted behavioral analyses on these mature animals and performed MR spectroscopy. Subsequently, all animals were sacrificed, and their brains were subject to biochemical and histological analysis. Our findings indicate that male rats exposed to the spike protein displayed a higher rate of impaired performance on behavioral studies, including the three-chamber social test, passive avoidance learning analysis, open field test, rotarod test, and novelty-induced cultivation behavior, indicative of autistic symptoms. Exposure to the spike protein (male) induced gliosis and neuronal cell death in the CA1-CA3 regions of the hippocampus and cerebellum. The spike protein-exposed male rats exhibited significantly greater levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and lactate and lower levels of brain-derived neurotrophic factor (BDNF) than the control group. Our study suggests a potential association between prenatal exposure to COVID-19 spike protein and neurodevelopmental problems, such as ASD. These findings highlight the importance of further research into the potential effects of the COVID-19 virus on embryonic and fetal development and the potential long-term consequences for neurodevelopment.
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Transtorno Autístico , COVID-19 , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Masculino , Gravidez , Ratos , Animais Recém-Nascidos , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/patologia , Modelos Animais de Doenças , Placenta/patologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
BACKGROUND: In stem cell applications, apart from bone marrow and adipose tissue, compact bone is also used as an alternative. However, studies on this subject are limited. In our study, we investigated the effect of stem cell derived from compact bone on rat zygomatic arch defect. METHODS: Fifteen rats were included in the study. Five rats were killed to obtain stem cells before the experiment. The rats were divided into 2 groups with 5 rats each. In group 1, compact bone-derived stem cell was applied. In group 2, adipose tissue-derived stem cell was applied. Right zygomatic arch defect was created in rats in both groups. Zygomatic bones were decellularized by cryosurgery. Stem cells were transferred to zygomatic bones. The number of stem cells, stem cell differentiation, and superficial markers obtained from the groups were examined. Histologically, cell structure, osteocyte count and osteopontin scores, elemental composition of the groups, percentages of resemblance to intact bone, osteocytes numbers, and cells were examined by electron microscopy of the bones in the groups after killing. RESULTS: The number of stem cells administered to the groups was 5 × 107 and 3.2 × 107 for group 1 and group 2, respectively (P > 0.05). Histologically, the morphology of the cells in group 1 was found to be healthier than group 2. The number of osteocytes was 97.56 ± 15.4 and 132.93 ± 10.8 in group 1 and group 2, respectively (P < 0.05). The osteopontin score was 3.47 ± 0.73 and 65 ± 0.64 in group 1 and group 2, respectively (P < 0.05). In the electron microscope examination, the morphologies of the cells in group 1 were seen more normal. The Ca/P ratio of the groups was 1.51 and 1.59 in group 1 and group 2, respectively (P > 0.05). Osteocyte counts were 10.7 ± 2.8 and 6.1 ± 1.2 in group 1 and group 2, respectively (P < 0.05). Morphological similarity percentages to normal bone were 88.4% and 79.6% in group 1 and group 2, respectively (P > 0.05). CONCLUSION: Stem cells obtained from compact bone gave positive results in zygomatic arch defect. This method can also be used as an alternative in stem cell applications.
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Osteopontina , Zigoma , Ratos , Animais , Zigoma/cirurgia , Osteogênese , Células-Tronco , Osso Cortical , Diferenciação CelularRESUMO
The study investigated the effects of ozone treatment on the neurodegeneration of stereotaxic rotenone-induced parkinson's disease (PD) model. The model was confirmed using the apomorphine rotation test. α-synuclein, amyloid-ß, Tau, phosphorylated Tau, as well as tyrosine hydroxylase(+), nNOS(+), and glial cell counts were used to evaluate neurodegeneration in the substantia nigra pars compacta and ventral tegmental area. The experiment involved 48 Sprague-Dawley rats divided into four groups: dimethyl sulfoxide (DMSO), DMSO with ozone (O), DMSO/rotenone (R), and D/R/O. Ozone treatment significantly improved tissue α-synuclein level and TH+, nNOS+, and glial cell counts compared to the rotenone-only group. The study suggests that ozone treatment may have beneficial effects on PD biomarkers in the rotenone model. Further studies on ozone dosage, duration, and administration methods in humans could provide more evidence for its potential use in Parkinson's disease treatment.
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Doença de Parkinson , Humanos , Ratos , Animais , Doença de Parkinson/tratamento farmacológico , Rotenona , alfa-Sinucleína/metabolismo , Ratos Sprague-Dawley , Dimetil Sulfóxido/farmacologia , Substância Negra/metabolismo , Modelos Animais de DoençasRESUMO
OBJECTIVE: This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. METHODS: This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. RESULTS: G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. CONCLUSION: In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.
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Purpose The aim of this study is to investigate the benefits of atorvastatin on the propionic acid-induced autism model via increasing sphingosine-1-phosphate and anti-inflammatory actions with imaging and brain tissue investigations. Materials and methods Twenty-five mg/kg/day/rat of propionic acid (PPA) was administered intraperitoneally to 20 male Wistar rats, and 10 male Wistar rats were fed orally. Study groups were designed as follows: Group 1: Control Group (orally fed control, n=10); Group 2 (PPA+saline, n=10); Group 3 (PPA+Atorvastatin, n=10). The brain biochemical and histopathology assessments and magnetic resonance (MR) imaging were conducted across groups in order to compare them. Results The PPA+Atorvastatin group was found to have significantly lower levels of brain malondialdehyde, IL-2 level, IL-17, tumor necrosis factor-alpha (TNF-α), and lactate compared to the PPA+saline group. The PPA+Atorvastatin group had higher levels of nerve growth factor and nuclear factor erythroid 2-related factor 2 (NRF-2) and sphingosine-1-phosphate. In histopathology assessments, the PPA+Atorvastatin group was found to have significantly higher neuronal counts of CA1 and CA2 in the hippocampus, and Purkinje cells in the cerebellum. Conclusions Current findings suggest that atorvastatin increases sphingosine-1-phosphate levels and decreases inflammatory actions which characterize the autism rodent model implemented in this study. These preliminary results have to be confirmed by further experimental and clinical studies.
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To evaluate the ameliorating effect of Modafinil on neuroinflammation, behavioral, and histopathological alterations in rats induced by propionic acid (PPA). Thirty male Wistar rats were used in the study, divided into 3 groups of ten subjects. One group served as a control, the subjects in the other two were given 250 mg/kg/day of PPA by intraperitoneal injection over the course of 5 days to induce autism. The experimental design was as follows: Group 1: Normal control (orally-fed control, n = 10); Group 2 (PPA + saline, n = 10): PPA and 1 ml/kg/day % 0.9 NaCl saline via oral gavage; Group 3 (PPA + Modafinil, n = 10) PPA and 30 mg/kg/day Modafinil (Modiodal tablets 100 mg, Cephalon) via oral gavage. All of the groups were investigated for behavioral, biochemical, and histological abnormality. Autism-like behaviors were reduced significantly in the rats treated with PPA. TNF-α, Nerve Growth Factor (NGF), IL-17, IL-2, and NF-KB levels as well as MDA levels and lactate were significantly higher in those treated with PPA compared to the control group. Using immunohistochemical methods, the number of neurons and GFAP immunoreactivity was significantly altered in PPA-treated rats compared to the control. Using Magnetic Resonance Spectroscopy (MRS), we found that lactate levels were significantly higher in the PPA-treated rats, while creatinine levels were significantly decreased. In the rats administered with Modafinil, behavior, neuroinflammation, and histopathological changes brought about by PPA were significantly reversed. Our results demonstrate the potential role of Modafinil in ameliorating PPA-induced neuroinflammation in rats.
Assuntos
Transtorno Autístico , Ratos , Masculino , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/metabolismo , Modafinila/efeitos adversos , Doenças Neuroinflamatórias , Ratos Wistar , Lactatos/efeitos adversosRESUMO
The aim of this research was to develop technetium-99m ([99mTc]Tc)-radiolabeled niosomes and evaluate the cancer cell incorporation capacity of radiolabeled niosomes. For this purpose, niosome formulations were developed by film hydration method, and prepared niosomes were characterized to particle size, polydispersity index (PdI), ζ-potential value, and image profile. Then, niosomes were radiolabeled with [99mTc]Tc using stannous salts (chloride) as a reducing agent. The radiochemical purity (RP) and stability in different mediums of the niosomes were assessed by ascending radioactive thin-layer chromatography (RTLC) and radioactive ultrahigh-performance liquid chromatography (R-UPLC) methods. Also, the partition coefficient value of radiolabeled niosomes was determined. The cell incorporation of [99mTc]Tc-labeled niosome formulations, as well as reduced/hydrolyzed (R/H)-[99mTc]NaTcO4 in the HT-29 (human colorectal adenocarcinoma) cells, was then assessed. According to the obtained results, the spherical niosomes had a particle size of 130.5 ± 1.364 nm, a PdI value of 0.250 ± 0.023, and a negative charge of -35.4 ± 1.06 mV. The niosome formulations were effectively radiolabeled with [99mTc]Tc using 500 µg mL-1 stannous chloride for 15 min, and RP was found to be over 95%. [99mTc]Tc-niosomes showed good in vitro stability in every system for up to 6 h. The logâ¯P value of radiolabeled niosomes was found as -0.66 ± 0.02. Compared to R/H-[99mTc]NaTcO4 (34.18 ± 1.56%), the incorporation percentages of [99mTc]Tc-niosomes (88.45 ± 2.54%) were shown to be higher in cancer cells. In conclusion, the newly developed [99mTc]Tc-niosomes showed good prototype for potential use in nuclear medicine imaging in the near future. However, further investigations, such as drug encapsulation and biodistribution studies, should be performed, and our studies are continuing.