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INTRODUCTION: Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide with various physiological functions. Escherichia coli is one of the most desirable hosts for recombinant protein production, especially for human proteins whose post-translation modifications are not essential for their bioactivity, such as hIGF-1. OBJECTIVES: In this study, bacterial thioredoxin (Trx) was studied as a fused and non-fused protein to convert the insoluble form of recombinant human IGF-1 (rhIGF-1) to its soluble form in E. coli. METHODS: The rhIGF-1 was expressed in the E. coli Origami strain in the form of fused-Trx. It was co-expressed with Trx and then purified and quantified. In the next step, the biological activity of rhIGF-1 was evaluated by alkaline phosphatase (ALP) activity assay in human adipose-derived stem cells (hASCs) regarding the differentiation enhancement effect of IGF-1 through the osteogenic process. RESULTS: Results showed that Trx in both the fused and non-fused forms had a positive effect on the production of the soluble form of rhIGF-1. A significant increase in ALP activity in hASCs after rhIGF-1 treatment was observed, confirming protein bioactivity. CONCLUSION: It was strongly suggested that the overproduction of Trx could increase the solubility of co-expressed recombinant proteins by changing the redox state in E. coli cells.
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INTRODUCTION: Biotinidase deficiency (BD) is an inherited autosomal recessive metabolic disorder. BD has been associated with optic nerve atrophy, eye infections, and retinopathy. The most prevalent ophthalmic manifestation of BD is optic atrophy, which might be misdiagnosed as multiple sclerosis or neuromyelitis optica, especially in late-onset BD cases. METHODS: In this article, we report a 9-year-old boy with gradual vision loss. Ophthalmologic examination, Brain MRI, and several laboratory tests such as Aquaporin-4 IgG level and biotinidase level were done on the patient. RESULTS: Bilateral optic atrophy and impaired visual acuity were detected on examination. The patient had a biotin level of 1.25 U/min/ml (normal range 3-9 U/min/ml), favoring the BD. CONCLUSION: In this study, we report a 9-year-old boy with vision loss diagnosed with BD. We also reviewed the literature to highlight the ophthalmic manifestations of BD. Ophthalmologists must consider BD in children with unexplained ophthalmologic complaints, especially when other characteristic signs of BD (e.g., developmental delay, seizure) are present. Also, patients with BD should undergo regular annual ophthalmologic examinations to be checked for any signs of eye involvement.
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Deficiencia de Biotinidasa , Atrofia Óptica , Masculino , Niño , Humanos , Deficiencia de Biotinidasa/complicaciones , Deficiencia de Biotinidasa/diagnóstico , Biotinidasa , Biotina , Trastornos de la VisiónRESUMEN
Current pharmacological treatments against post-traumatic stress disorder (PTSD) lack adequate efficacy. As a result, intense research has focused on identifying other molecular pathways mediating the pathogenesis of this condition. One such pathway is neuroinflammation, which has demonstrated a role in PTSD pathogenesis by causing synaptic dysfunction, neuronal death, and functional impairment in the hippocampus. Phosphodiesterase (PDE) inhibitors (PDEIs) have emerged as promising therapeutic agents against neuroinflammation in other neurological conditions. Furthermore, PDEIs have shown some promise in animal models of PTSD. However, the current model of PTSD pathogenesis, which is based on dysregulated fear learning, implies that PDE inhibition in neurons should enhance the acquisition of fear memory from the traumatic event. As a result, we hypothesized that PDEIs may improve PTSD symptoms through inhibiting neuroinflammation rather than long-term potentiation-related mechanisms. To this end, we tested the therapeutic efficacy of cilostazol, a selective inhibitor of PDE3, on PTSD-related anxiety symptoms in the underwater trauma model of PTSD. PDE3 is expressed much more richly in microglia and astrocytes compared to neurons in the murine brain. Furthermore, we used hippocampal indolamine 2,3-dioxygenase 1 (IDO) expression and interleukin 1 beta (IL-1ß) concentration as indicators of neuroinflammation. We observed that cilostazol pretreatment prevented the development of anxiety symptoms and the increase in hippocampal IDO and IL-1ß following PTSD induction. As a result, PDE3 inhibition ameliorated the neuroinflammatory processes involved in the development of PTSD symptoms. Therefore, cilostazol and other PDEIs may be promising candidates for further investigation as pharmacological therapies against PTSD.
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Trastornos por Estrés Postraumático , Ratones , Animales , Cilostazol/farmacología , Cilostazol/uso terapéutico , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/prevención & control , Trastornos por Estrés Postraumático/metabolismo , Enfermedades Neuroinflamatorias , Ansiedad/tratamiento farmacológico , Ansiedad/prevención & control , Hipocampo/metabolismoRESUMEN
BACKGROUND: Congenital simple hamartoma of the retinal pigment epithelium is often identified as an incidental finding. One important issue is the differentiation of these benign lesions from other lesions which could be potentially sight-threatening. METHODS: This study describes 4 cases of congenital simple hamartoma of the retinal pigment epithelium that were referred to a university-based hospital. Multimodal imaging including fundus photo, multicolor fundus photo, fundus autofluorescence, optical coherence tomography (OCT), OCT angiography, fluorescein angiography and multifocal electroretinogram is provided. RESULTS: The first case is a young man with an incidental finding of this lesion. The second and third cases are diabetic patients with congenital simple hamartoma of the retinal pigment epithelium and diabetic macular edema and the fourth one is a case of congenital simple hamartoma of the retinal pigment epithelium with a full-thickness macular hole. CONCLUSIONS: Differentiation of congenital simple hamartoma of the retinal pigment epithelium from other potentially sight-threatening lesions is important. Multimodal imaging can be helpful regarding this issue. Besides typical findings described in the literature, unique features in our cases include concurrent diabetic macular edema and association with a full-thickness macular hole.
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Retinopatía Diabética , Hamartoma , Edema Macular , Enfermedades de la Retina , Perforaciones de la Retina , Masculino , Humanos , Epitelio Pigmentado de la Retina/patología , Perforaciones de la Retina/patología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/complicaciones , Edema Macular/patología , Retinopatía Diabética/complicaciones , Angiografía con Fluoresceína , Hamartoma/diagnóstico , Hamartoma/complicaciones , Imagen Multimodal , Tomografía de Coherencia Óptica/métodosRESUMEN
OBJECTIVE: To compare the incidence of falls between patients with visually significant cataracts in both eyes and those who have undergone first-eye cataract surgery. METHODS: This retrospective case-control study involved patients with a history of cataracts in both eyes who had undergone first-eye cataract surgery within the past 9 to 12 months (pseudophakic group). The control group comprised patients with cataracts in both eyes (cataract group). We assessed best-corrected visual acuity (BCVA), systemic comorbidities and medications (using the Charlson comorbidity index), and independent daily activities (using the Lawton Instrumental Activities of Daily Living scale). The patients were questioned about experiencing two or more falls in the last 6 months. RESULTS: Each group comprised 50 patients. Binocular BCVA was significantly better in the pseudophakic group (0.05 ± 0.06 logMAR) than in the cataract group (0.77 ± 0.34 logMAR). Of all participants, 22% reported experiencing two or more falls in the last 6 months. Multivariate analysis demonstrated significantly better BCVA in participants with less than two falls. CONCLUSIONS: Patients of advanced age with visually significant cataracts in both eyes are at a higher risk of falling. First-eye cataract surgery may mitigate the occurrence of falls by improving binocular BCVA.
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Catarata , Facoemulsificación , Humanos , Accidentes por Caídas , Estudios Retrospectivos , Estudios de Casos y Controles , Actividades Cotidianas , Agudeza Visual , Catarata/complicacionesRESUMEN
Pediatric rhegmatogenous retinal detachment (RRD) is an issue of debate regarding its surgical outcomes and prognosis because of diagnosis delay, more complex etiological factors, and a higher prevalence of postoperative complications. This meta-analysis aims to evaluate the anatomical and visual outcomes of pediatric RRD and the factors that influence the treatment results. This is the first meta-analysis on this subject. We searched the relevant publications in the electronic databases of PubMed, Scopus, and Google Scholar. Eligible studies were included in the analysis. Anatomical success after one surgery and the final rates of success were estimated. Subgroup analysis was performed to find the rate of success in patients with different prognostic factors. This meta-analysis showed that the total rate of success after one surgery was about 64%, which implies that performing the first surgery was enough to get anatomical reattachment in most of the patients. The final anatomical rate of success was about 84%. In terms of visual acuity, the pooled results revealed statistically significant (P < 0.001) improvement in postoperative vision, with a 0.42 reduction in log of minimum angle of resolution (logMAR). The final rate of success was significantly lower in eyes with proliferative vitreoretinopathy (PVR) (about 25% lower in eyes with PVR, P < 0.001) and in the presence of congenital anomalies (about 36% lower in congenital cases, P = 0.008). Myopic RRD had a significantly better anatomical success rate. In conclusion, this study shows that there is a high chance of anatomical success after pediatric RRD treatment. The presence of PVR and congenital anomalies was associated with a poorer prognosis.
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Miopía , Desprendimiento de Retina , Vitreorretinopatía Proliferativa , Humanos , Niño , Pronóstico , OjoRESUMEN
Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.
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Neuralgia , Espermidina , Ratas , Masculino , Animales , Espermidina/farmacología , Constricción , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Umbral del Dolor , Nervio Ciático , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiologíaRESUMEN
Cystoid macular oedema (CMO), which is defined as a macular thickening and cystic changes due to accumulation of fluid, could be asymptomatic and only diagnosed using paraclinical techniques. Fluorescein angiography (FA) and optical coherence tomography (OCT) are useful in detecting CMO in clinical practice. Non-leaking CMO, also known as angiographically silent CMO, is referred to as cases of CMO without leakage in fluorescein angiography. This type of CMO has been reported in some retinal dystrophies, in cases of maculopathy as a side effect of certain drugs, and also in some systemic disorders. The exact mechanism and treatment options for this type of CMO are still not clear. This literature review aims to discuss different causes of non-leaking CMO, proposed mechanisms, and management options. Three sections including drugs, retinal dystrophies, and systemic disorders are discussed in this review.
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Edema Macular , Distrofias Retinianas , Humanos , Edema Macular/diagnóstico por imagen , Edema Macular/etiología , Angiografía con Fluoresceína , Retina , Tomografía de Coherencia Óptica , Distrofias Retinianas/complicacionesRESUMEN
While SSRIs are the current first-line pharmacotherapies against post-traumatic stress disorder (PTSD), they suffer from delayed onset of efficacy and low remission rates. One solution is to combine SSRIs with other treatments. Neuronal nitric oxide synthase (nNOS) has been shown to play a role in serotonergic signaling, and there is evidence of synergism between nNOS modulation and SSRIs in models of other psychiatric conditions. Therefore, in this study, we combined subchronic fluoxetine (Flx) with 7-nitroindazole (NI), a selective nNOS inhibitor, and evaluated their efficacy against anxiety-related behavior in an animal model of PTSD. We used the underwater trauma model to induce PTSD in rats. Animals underwent the open field (OFT) and elevated plus maze tests on days 14 (baseline) and 21 (post-treatment) after PTSD induction to assess anxiety-related behaviors. Between the two tests, the rats received daily intraperitoneal injections of 10 mg/kg Flx or saline, and were injected intraperitoneally before the second test with either 15 mg/kg NI or saline. The change in behaviors between the two tests was compared between treatment groups. Individual treatment with both Flx and NI had anxiogenic effects in the OFT. These effects were associated with modest increases in cFOS expression in the hippocampus. Combination therapy with Flx + NI did not show any anxiogenic effects, while causing even higher expression levels of cFOS. In conclusion, addition of NI treatment to subchronic Flx therapy accelerated the abrogation of Flx's anxiogenic properties. Furthermore, hippocampal activity, as evidenced by cFOS expression, was biphasically related to anxiety-related behavior.
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Ansiolíticos , Inhibidores Enzimáticos , Óxido Nítrico Sintasa de Tipo I , Inhibidores Selectivos de la Recaptación de Serotonina , Trastornos por Estrés Postraumático , Animales , Ratas , Ansiedad/metabolismo , Modelos Animales de Enfermedad , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Hipocampo/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo I/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/metabolismo , Quimioterapia Combinada , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Ansiolíticos/farmacología , Ansiolíticos/uso terapéuticoRESUMEN
BACKGROUND: Long-term complications of stroke, persisting for more than 6 months after the initial event, substantially reduce the quality of life (QoL) in a significant percentage of stroke survivors. In this paper, we studied the prevalence of long-term urinary incontinence (UI) in post-stroke patients. In addition, we attempted to identify patient characteristics which were associated with higher UI prevalence, higher UI severity, and less UI-associated QoL. METHODS: Medical records in a tertiary referral hospital were used to contact patients who had experienced a stroke between 6 to 32 months before the study date. The patients were given the International Consultation on Incontinence Questionnaire Short Form (ICIQ-UI-SF) questionnaire for determining the presence of UI and its severity. UI-positive patients were then given the I-QOL questionnaire to determine their QoL. RESULTS: The prevalence of UI in our study population (n=189) was 31%. Older age at the time of stroke was associated with higher UI severity (r=0.290) and lower QoL (r=-0.265). Furthermore, the presence of movement limitation was associated with higher UI prevalence (P<0.001, OR=3.89) and severity (P=0.002, d=1.05). Movement limitation also significantly impacted the psychological and social aspects of UI-associated QoL (P=0.035, d=-0.74). Conversely, higher body mass indices (BMIs) were associated with lower UI severity (r=-0.346) and higher QoL (r=0.281). CONCLUSION: In conclusion, UI continues to be prevalent in stroke survivors long after the cerebrovascular accident (CVA). As a result, these patients require continuous monitoring and UI prevention.
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Accidente Cerebrovascular , Incontinencia Urinaria , Humanos , Calidad de Vida , Estudios Retrospectivos , Prevalencia , Incontinencia Urinaria/epidemiología , Incontinencia Urinaria/etiología , Encuestas y Cuestionarios , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiologíaRESUMEN
Purpose: To report a rare case of Woakes' syndrome presented with bilateral vision loss. Methods: A 28-year-old male with a 1-year history of vision loss in the left eye was referred to the neuro-ophthalmology clinic after sudden vision loss in his right eye. A detailed review of clinical findings and the presumed pathophysiological basis of vision loss was performed. Results: Neuroimaging revealed bilateral massive nasal polyps, sphenoid sinus mucocele formation, and optic nerve dehiscence inside the sphenoid sinus. The vision in the right eye was restored after pulse corticosteroid therapy; however, the left eye remained severely visually compromised even after nasal polypectomy and mucocele drainage. Conclusion: Sinonasal disorders should be sought for patients with unexplained vision loss, as prompt intervention could be vision-saving in these patients.
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We describe a technique for metallic intralenticular foreign body (ILFB) removal in a patient in whom there was no or minimal cataract formation or other complications. This technique required creating two corneal small incisions around the ILFB for inserting iris retractors to expose the ILFB. At the foreign body position, a clear corneal incision was made, and then the ILFB was removed with minimal manipulation by an intraocular magnet without complications. Because most occupational traumas occur in young people, this technique avoids the adverse outcomes of lens extraction in this age group.
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Extracción de Catarata , Catarata , Cuerpos Extraños en el Ojo , Cristalino , Adolescente , Extracción de Catarata/efectos adversos , Cuerpos Extraños en el Ojo/complicaciones , Cuerpos Extraños en el Ojo/cirugía , Humanos , Implantación de Lentes Intraoculares/efectos adversos , Cristalino/cirugíaRESUMEN
RATIONALE: Current pharmacological approaches to treatment of post-traumatic stress disorder (PTSD) lack adequate effectiveness. As a result, identifying new molecular targets for drug development is necessary. Furthermore, fear learning and memory in PTSD can undergo different phases, such as fear acquisition, consolidation, and extinction. Each phase may involve different cellular pathways and brain regions. As a result, effective management of PTSD requires mindfulness of the timing of drug administration. One of the molecular targets currently under intense investigation is the N-methyl-D-aspartate (NMDA)-type glutamate receptor (NMDAR). However, despite the therapeutic efficacy of drugs targeting NMDAR, their translation into clinical use has been challenging due to their various side effects. One possible solution to this problem is to target signaling proteins downstream to NMDAR to improve targeting specificity. One of these proteins is the neuronal nitric oxide synthase (nNOS), which is activated following calcium influx through the NMDAR. OBJECTIVE: In this paper, we review the literature on the pharmacological modulation of nNOS in animal models of PTSD to evaluate its therapeutic potential. Furthermore, we attempt to decipher the inconsistencies observed between the findings of these studies based on the specific phase of fear learning which they had targeted. RESULTS: Inhibition of nNOS may inhibit fear acquisition and recall, while not having a significant effect on fear consolidation and extinction. However, it may improve extinction consolidation or reconsolidation blockade. CONCLUSIONS: Modulation of nNOS has therapeutic potential against PTSD and warrants further development for use in the clinical setting.
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Trastornos por Estrés Postraumático , Animales , Calcio/metabolismo , Extinción Psicológica/fisiología , N-Metilaspartato/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Trastornos por Estrés Postraumático/tratamiento farmacológicoRESUMEN
Introduction: B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (PRDM1), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. Methods: In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation. Specifically, we investigated the role of BLIMP1 in memory differentiation and exhaustion of human T cells. We used CRISPR interference (CRISPRi) to knock-down BLIMP1 and investigated the differential expressions of T cell memory and exhaustion markers in BLIMP1-deficient T cells in comparison with BLIMP1-sufficient ex vivo expanded human T cells. Results: BLIMP1-deficiency caused an increase in central memory (CM) T cells and a decrease in effector memory (EM) T cells. There was a decrease in the amount of TIM3 exhaustion marker expression in BLIMP1-deficient T cells; however, there was an increase in PD1 exhaustion marker expression in BLIMP1-deficient T cells compared with BLIMP1-sufficient T cells. Conclusion: Our study provides the first functional evidence of the impact of BLIMP1 on the regulation of human T cell memory and exhaustion phenotype. These findings suggest that BLIMP1 may be a promising target to improve the immune response in adoptive T cell therapy settings.
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BACKGROUND: Chorioretinal coloboma is a congenital anomaly which can be present in a clinical spectrum with a possibility of significant influence on visual acuity. Optical coherence tomography (OCT) has been frequently used for the study of chorioretinal coloboma. OCT angiography (OCTA), as a non-invasive method of taking high-resolution images of chorioretinal vessels, can improve our understanding of developmental aspects of this anomaly. MATERIALS AND METHODS: This observational case series evaluated patients with chorioretinal coloboma, who were referred to the eye clinic of a university-based hospital between March 2018 and October 2019. All patients underwent comprehensive ocular examination, OCT, and OCTA using AngioVue technologies from the colobomatous sites. RESULTS: This study included OCTA imaging of five patients (six eyes) with chorioretinal coloboma lesions. Large retinal vessels, which were intact in all eyes, coursed through the coloboma in four cases and around the margin of the involved area in one case. Attenuation of the microvasculature in the vicinity of coloboma with various extents from nearly normal to severe attenuation was evident in OCTA. Five eyes of four patients had disorganized superficial vessel plexus. Also corkscrew vessels were found in one eye. CONCLUSIONS: This is the first study assessing the vascular pattern in the vicinity of chorioretinal coloboma using OCTA. OCTA revealed nearly normal to severely attenuated retinal microvasculature. At the same time, intact large retinal vessels at the level of superficial vessel plexus coursed across or around the coloboma. OCTA imaging adds new insights about vascular characteristics in the vicinity of these lesions.
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Coloboma , Enfermedades de la Retina , Coroides/anomalías , Coloboma/diagnóstico , Coloboma/patología , Angiografía con Fluoresceína/métodos , Humanos , Enfermedades de la Retina/patología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND AND AIM: Epigenetic modifications exhibit promising evidence in etiology and prognosis of important diseases such as inflammatory bowel diseases (IBD). In addition to complex factors involved in IBD, a trend toward better prognosis have been reported in older ages of disease onset. Gastrointestinal mucous layer is one of the important components which is disturbed in the disease course. Integrity of this layer is maintained with an anti-inflammatory factor called trefoil factors (TFF). We investigated the methylation status of TFF1 gene in IBD patients alongside with correlation of its alteration level with age of disease onset. METHODS: We analyzed the promoter methylation status of TFF1 gene, using the real-time quantitative multiplex methylation specific PCR (QM-MSP). DNA was extracted from colorectal biopsies of 15 Crohn disease cases and 15 healthy controls. Correlation analysis was performed between unmethylated DNA level and age through Pearson correlation coefficient (PPC) test and simple linear regression models. RESULTS: Our data didn't provide significant positive correlation of age and TFF1 hypomethylation in Crohn patients (r = .518, p = .058). CONCLUSIONS: In conclusion, our case-control study didn't show significant alteration in TFF1 methylation status in CD patients. (www.actabiomedica.it).
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Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Estudios de Casos y Controles , Enfermedad de Crohn/genética , Humanos , Péptidos/genética , Factor Trefoil-1/genética , Factor Trefoil-2Asunto(s)
Enfermedades de la Retina , Oclusión de la Vena Retiniana , Enfermedades Hereditarias del Ojo , Heterocigoto , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Mutación , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/genéticaRESUMEN
AIMS: Allergic rhinitis (AR), a major chronic inflammatory disease of the respiratory system, is a public health issue because of its substantial negative impact on quality of life and work efficiency alongside its high prevalence and costs. Dapsone is a sulfone chemical with reported anti-inflammatory and antibacterial properties. Accordingly, we investigated the anti-inflammatory impact of dapsone on ovalbumin-induced allergic rhinitis in balb/c mice. MAIN METHODS: Intraperitoneal ovalbumin and hydroxide aluminum injection followed by intranasal ovalbumin administration sensitized female Balb/c mice. Mice received intraperitoneal dapsone either acute (5, 10, 20 mg/kg) 30 min before the last ovalbumin challenge, or chronic (20 mg/kg) on days 21 to 35. KEY FINDINGS: Both acute and chronic intraperitoneal usage of dapsone showed a considerable decrease in the nasal scratching behavior, the number of sneezing, serum IL-4 and IgE levels of ovalbumin-induced AR in balb/c mice, but there was a significant increase in serum IFNγ level. Histopathological analysis demonstrated a significant reduction of eosinophil numbers, following dapsone injection. Goblet cell hyperplasia and respiratory epithelial-thickness decreased significantly in the acute and chronic 20 mg/kg dapsone groups compared to the ovalbumin-induced controls. SIGNIFICANCE: This study shows that there is an association between acute and chronic dapsone treatment and some anti-allergic effects through an inflammation cascade.
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Dapsona , Rinitis Alérgica , Animales , Citocinas/farmacología , Dapsona/efectos adversos , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Mucosa Nasal/patología , Ovalbúmina/efectos adversos , Calidad de VidaRESUMEN
The liver detoxifies and metabolizes many drugs and xenobiotics which may cause hepatotoxicity due to some toxic agents. Carbon tetrachloride (CCl4) is metabolized in cytochrome P450 and its reactive radical metabolites cause lipid peroxidation, cellular injury, and apoptosis. Sumatriptan (SUM), 5-HT1B/1D receptor agonist, had anti-inflammatory and anti-oxidant effects. In this research the effect of SUM pre-treatment against CCl4-induced hepatotoxicity was examined. Adult rats received SUM (0.1, 0.3 and 1 mg/kg; i.p.) for 3 consecutive days before CCl4 (2 ml/kg; i.p. on the 3rd day). The aminotransferases serum levels, tissue levels of anti-oxidant and pro-inflammatory markers and histopathological examination were evaluated. SUM (0.3 mg/kg) prevented significantly the elevation of aminotransferases versus the control group (CCl4 group) (P<0.0001) and also, reversed meaningfully the changes of the MPO, MDA, SOD and CAT, IL-1ß and TNF-α levels. Additionally, CCl4-intoxication resulted to the disruption of lobular and cellular structures and inflammation in histopathological evaluation which is prevented by SUM (0.3 mg/kg). These data revealed that SUM (0.3 mg/kg), but no at doses 0.1 and 1 mg/kg, decreases the hepatotoxicity of induced by CCl4 in rats.
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Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Peroxidación de Lípido , Hígado/metabolismo , Estrés Oxidativo , Ratas , Sumatriptán/farmacologíaRESUMEN
Depression is the most common psychiatric comorbidity of epilepsy. However, the molecular pathways underlying this association remain unclear. The NMDA receptor (NMDAR) may play a role in this association, as its downstream signaling has been shown to undergo long-term changes following excitotoxic neuronal damage. To study this pathway, we used an animal model of fluoxetine-resistant epilepsy-associated depression (EAD). We determined the molecular changes associated with the development of depressive symptoms and examined their response to various combinations of fluoxetine and a selective neuronal nitric oxide synthase inhibitor, 7-nitroindazole (NI). Depressive symptoms were determined using the forced swim test. Furthermore, expression and phosphorylation levels of markers in the ERK/CREB/ELK1/BDNF/cFOS pathway were measured to determine the molecular changes associated with these symptoms. Finally, oxidative stress markers were measured to more clearly determine the individual contributions of each treatment. While chronic fluoxetine (Flxc) and NI were ineffective alone, their combination had a statistically significant synergistic effect in reducing depressive symptoms. The development of depressive symptoms in epileptic rats was associated with the downregulation of ERK2 expression and ELK1 and CREB phosphorylation. These changes were exactly reversed upon Flxc + NI treatment, which led to increased BDNF and cFOS expression as well. Interestingly, ERK1 did not seem to play a role in these experiments. NI seemed to have augmented Flxc's antidepressant activity by reducing oxidative stress. Our findings suggest NMDAR signaling alterations are a major contributor to EAD development and a potential target for treating conditions associated with underlying excitotoxic neuronal damage.