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1.
Toxicol Res (Camb) ; 12(6): 1063-1076, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145093

RESUMO

This study evaluates whether elderberry (EB) effectively decreases the inflammation and oxidative stress in the brain cells to reduce Aß toxicity. In the Aß + EB group, EB powder was added to rats' routine diet for eight consecutive weeks. Then, spatial memory, working memory, and long-term memory, were measured using the Morris water maze, T-maze, and passive avoidance test. Also, in this investigation immunohistopathology, distribution of hippocampal cells, and gene expression was carried out. Voronoi tessellation method was used to estimate the spatial distribution of the cells in the hippocampus. In addition to improving the memory functions of rats with Aß toxicity, a reduction in astrogliosis and astrocytes process length and the number of branches and intersections distal to the soma was observed in their hippocampus compared to the control group. Further analysis indicated that the EB diet decreased the caspase-3 expression in the hippocampus of rats with Aß toxicity. Also, EB protected hippocampal pyramidal neurons against Aß toxicity and improved the spatial distribution of the hippocampal neurons. Moreover, EB decreased the expression of inflammatory and apoptotic genes. Overall, our study suggest that EB can be considered a potent modifier of astrocytes' reactivation and inflammatory responses.

2.
Toxicol Res (Camb) ; 12(6): 1077-1094, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145099

RESUMO

The present study aimed to elucidate the effect of 10 mg/kg Δ9-tetrahydrocannabinol (THC) on cerebellar neuronal and glial morphology, apoptosis and inflammatory gene expression using a series of histological assays including stereology, Sholl analysis, immunofluorescence and real-time qPCR in male Wistar rats. A decrease in the number of Purkinje neurons and the thickness of the granular layer in the cerebellum was reported in THC-treated rats. Increased expression of Iba-1 and arborization of microglial processes were evidence of microgliosis and morphological changes in microglia. In addition, astrogliosis and changes in astrocyte morphology were other findings associated with THC administration. THC also led to an increase in caspase-3 positive cells and a decrease in autophagy and inflammatory gene expression such as mTOR, BECN1 and LAMP2. However, there were no significant changes in the volume of molecular layers and white matter, the spatial arrangement of granular layers and white matter, or the spatial arrangement of granular layers and white matter in the cerebellum. Taken together, our data showed both neuroprotective and neurodegenerative properties of THC in the cerebellum, which require further study in the future.

3.
Clin Biochem ; 121-122: 110684, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37944628

RESUMO

Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in otolaryngology. Various biomarkers have been used to determine the prognosis of SSNHL. This systematic review and meta-analysis aims to evaluate the relationship between the different biomarkers and the prognosis of SSNHL. We searched English-language literature up to October 2022 in four databases, including PubMed, Google Scholar, Cochrane, and Science Direct. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study was reported in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID = CRD42022369538). All studies examining the role of neutrophil to lymphocyte ratio (NLR) concluded that higher NLR is associated with a worse prognosis. The results of studies regarding the relationship between platelet to lymphocyte ratio (PLR) and tumor necrosis factor (TNF) are controversial. Other factors shown to be associated with SSNHL include Glycated hemoglobin (HbA1C), blood glucose, iron levels, serum endocan, salusin-beta, and bone turnover biomarkers. This meta-analysis showed that PLR, NLR, and neutrophils were significantly different between recovered and non-recovered patients. PLR, NLR, and neutrophil count are reliable tools to assess the prognosis of patients with SSNHL.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Biomarcadores , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/diagnóstico , Linfócitos , Neutrófilos , Prognóstico
4.
Acta Parasitol ; 68(4): 880-890, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37924457

RESUMO

BACKGROUND: Toxoplasmosis is a cosmopolitan parasitic infection caused by Toxoplasma gondii which is commonly treated by pyrimethamine (PYR) plus sulfadiazine (SDZ) with several adverse side effects. The present study evaluated the therapeutic effects of Urtica dioica L. aqueous extract (UDE) on acute and chronic toxoplasmosis in mice. METHODS: For this purpose, mice were infected with 20 cysts (acute infection) or 10 cysts (chronic infection) of T. gondii (Me49 strain). The mice were treated with 200 mg/kg of UDE intraperitoneally (IP) and intragastric route (IG). The UDE-treated mice were compared with the PYR + SDZ treatment. The histopathological changes, cyst count, total antioxidant capacity (TAC), malondialdehyde (MDA) assay, and serum INF-γ were also evaluated. RESULTS: In the acute toxoplasmosis, UDE by IP and IG administration significantly reduced the number of brain cysts by 93.74 and 92.55%, respectively, and increased the survival rate to 80% compared with 60% in untreated controls. In the chronic infection, cyst burden decreased at 88.2 and 83.4%, respectively, for IP and IG treatments. Moreover, UDE significantly increased INF- γ levels in acute and chronic toxoplasmosis. Tissue inflammatory lesions were reduced in the UDE-treated subgroups compared to the untreated group. UDE treatment significantly reduced MDA levels and elevated TAC in both acute and chronic infections. CONCLUSION: The results show that U. dioica possesses significant immunostimulant and antioxidant activity with a higher cyst reduction in the brain during acute toxoplasmosis. Further studies are required to investigate the fractionations of UDE against T. gondii and its combination with other standard drugs.


Assuntos
Toxoplasma , Toxoplasmose Animal , Toxoplasmose , Urtica dioica , Animais , Camundongos , Antioxidantes/farmacologia , Infecção Persistente , Toxoplasmose/parasitologia , Imunidade , Toxoplasmose Animal/tratamento farmacológico , Toxoplasmose Animal/parasitologia
5.
J Chem Neuroanat ; 126: 102172, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36280114

RESUMO

Reports have emerged on the sudden opioid-induced auditory hearing loss, and the underlying pathology is not fully understood. The present study aimed to determine the mechanism of action of these drugs in the inner ear. For this purpose, 20 rats were treated with 50 mg/kg tramadol daily for three weeks. Next, the stereological and immunohistochemical alteration of the inner hair cells under chronic exposure to tramadol was evaluated. The results revealed that tramadol induced hair cell degeneration and decreased bipolar neurons of the spiral ganglion and the thickness of stria vascularis. Moreover, immunohistochemistry showed that tramadol caused apoptosis in inner hair cells and bipolar neurons. These findings indicate that tramadol induces apoptosis in auditory hair cells, suggesting that tramadol may cause hearing loss and ototoxicity.


Assuntos
Perda Auditiva , Tramadol , Ratos , Masculino , Animais , Tramadol/toxicidade , Células Ciliadas Auditivas , Estria Vascular/patologia , Apoptose , Perda Auditiva/patologia
6.
Mol Cell Neurosci ; 121: 103752, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35781072

RESUMO

Hearing is mainly dependent on the function of hair cells (HCs) and spiral ganglion neurons (SGNs) which damage or loss of them leads to irreversible hearing loss. Olfactory ensheathing cells (OECs) are specialized glia that forms the fascicles of the olfactory nerve by surrounding the olfactory sensory axons. The OECs, as a regenerating part of the nervous system, play a supporting function in axonal regeneration and express a wide range of growth factors. In addition, retinoic acid (RA) enhances the proliferation and differentiation of these cells into the nerve. In the present study, we co-cultured human OECs (hOECs) with cochlear SGNs in order to determine whether hOECs and RA co-treatment can protect the repair process in gentamycin-induced SGNs damage in vitro. For this purpose, cochlear cultures were prepared from P4 Wistar rats, which were randomly appointed to four groups: normal cultivated SGNs (Control), gentamicin-lesioned SGNs culture (Gent), gentamicin-lesioned SGNs culture treated with OECs (Gent + OECs) and gentamicin-lesioned SGNs culture co-treated with OECs and RA (Gent + OEC& RA). The expression of a specific protein in SGNs was examined using immunohistochemical and Western blotting technique. TUNEl staining was used to detect cell apoptosis. Here, we revealed that combined treatment of OECs and RA protect synapsin and Tuj-1 expression in the lesioned SGNs and attenuate cell apoptosis. These findings suggest that RA co-treatment can enhance efficiency of OECs in repair of SGNs damage induced by ototoxic drug.


Assuntos
Gânglio Espiral da Cóclea , Tretinoína , Animais , Células Cultivadas , Gentamicinas/toxicidade , Humanos , Neurônios , Bulbo Olfatório , Ratos , Ratos Wistar , Tretinoína/farmacologia
7.
Med J Islam Repub Iran ; 35: 56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268244

RESUMO

Background: The overdose of illicit drugs is not always fatal but can lead to various complications. One of the unusual medical complications is a sensorineural hearing loss (SNHL). There are multiple case reports about this subject. Considering the importance of hearing loss on quality of life, we investigated hearing status in patients with overdose of illicit drugs. Methods: This cross-sectional study was performed in Loghman Hakim hospital in Shahid Beheshti University of Medical Sciences, Tehran, Iran, in 2016-2017. The hearing status of 95 patients with illicit drugs overdose and 44 healthy individuals were assessed using standard pure tone audiometry and distortion product otoacoustic emissions. The patient group was categorized based on hearing status and compared based on some variables. We applied 2 independent t tests, Mann-Whitney, Chi-square, and binary logistic regression tests. All analyses were conducted in Stata 12 (STATA Corp, USA) and significance level was set at less than 0.05. Results: We found higher percentage frequency of SNHL in the patient group than the control group (15.8% vs 2.3%; p=0.021). The frequency of hearing loss was 21.7% in opioid users, 5.3% in stimulant users, and 6.3% in concomitant use of both. There was a significant relationship between SNHL and overdose of illicit drugs (aOR = 14.48, 95% CI = 1.53-136.44; p=0.019) with adjusting age, sex, and smoking. Conclusion: Illicit drugs overdose can potentially affect the hearing system. Opioid drugs, especially methadone and tramadol, have been found to affect the hearing system. Therefore, it is important to conduct longitudinal studies to demonstrate the role of opioid drugs on the hearing system.

8.
J Chem Neuroanat ; 114: 101956, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33831513

RESUMO

Noise-induced hearing loss (NIHL) is the second most common cause of acquired hearing loss. Acoustic trauma can cause oxidative damage in the cochlear hair cells (HCs) through apoptotic pathways. Apelin is a newly discovered neuropeptide with neuroprotective effects against the oxidative stress in neurodegenerative disorder. We investigated the preventive effects of apelin-13 on the cochlear HCs and spiral ganglion neurons (SGNs) against acoustic trauma via Sirtuin-1 (Sirt-1) regulation in rats. Animals were assigned to control, control + apelin-13 (50 or 100 µg/kg, ip), and noise exposure groups without any treatment or were administered apelin-13 (50 or 100 µg/kg, ip) and EX-527 (an inhibitor of Sirt-1) prior to each noise session. In the noise groups, 110 dB white noise was applied for 6 h per 5 days. Pre- and post-exposure distortion product otoacoustic emissions (DPOAE) and cochlear superoxide dismutase (SOD) activity were assessed. Western blot evaluated the cochlear protein expressions of Sirt-1, cleaved-caspase-3, Bax, and Bcl-2. Cell apoptosis was detected through TUNEL staining. Immunofluorescence was used to examine expression of HCs and SGNs specific protein. DPOAE level were significantly improved in the noise exposure group receiving 100 µg/kg apelin-13. At high doses, apelin augmented SOD levels in the rat cochlea subjected to noise. Apelin 100 markedly increased Sirt-1, and decreased cleaved- caspase-3 expression as well as Bax/Bcl-2 ratio in the cochlea tissue of noise-exposed rats. These findings suggest the promising therapeutic potential of apelin-13 for the prevention of noise-induced injury to cochlea and hearing loss.


Assuntos
Cóclea/efeitos dos fármacos , Perda Auditiva Provocada por Ruído/patologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Fármacos Neuroprotetores/farmacologia , Sirtuína 1/biossíntese , Animais , Apoptose/efeitos dos fármacos , Cóclea/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Perda Auditiva Provocada por Ruído/metabolismo , Masculino , Ratos , Ratos Wistar
9.
Brain Res ; 1762: 147444, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33745925

RESUMO

Huntington's disease (HD) is an inherited neurodegenerative disorder which begins in the striatum and then spreads to other neural areas. Known as a progressive movement cognitive disorder, HD has no efficient therapy. Although the exact mechanism of HD is still unknown, several different etiological processes such as oxidative stress have been shown to play critical roles. Also, the current evidence indicates a strong correlation between immune activation and neural damage induced by neuroinflammatory and apoptotic agents in neurodegenerative disorders. Thus, natural products like Elderberry (EB) could be considered as a novel and potential therapeutic candidate for the treatment of this disease. In this study EB was added to the daily ration of ordinary rats for two months in order to ameliorate inflammatory and oxidative responses in rats injected with 3-nitropropionic acid (3-NP) in an experimental model of HD. Using Rotarod and electromyography setups, we showed that EB diet significantly recovered motor failure and muscle incoordination in 3-NP injected rats compared to the control group. Also, the molecular findings implied that EB diet led to a significant drop in 3-NP induced growth in caspase-3 and TNF-α concentration. The treatment also improved striatal antioxidative capacity by a significant reduction in ROS and a remarkable rise in GSH, which might be correlated with motor recovery in the tests. In sum, the findings demonstrate the advantages of EB treatment in the HD rat model with a score of beneficial anti-oxidative and anti-inflammatory effects.


Assuntos
Doença de Huntington/induzido quimicamente , Doença de Huntington/dietoterapia , Atividade Motora/fisiologia , Nitrocompostos/toxicidade , Estresse Oxidativo/fisiologia , Propionatos/toxicidade , Sambucus , Animais , Morte Celular/fisiologia , Modelos Animais de Doenças , Estimulação Elétrica/métodos , Eletromiografia/métodos , Doença de Huntington/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
11.
Iran J Child Neurol ; 13(2): 125-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037085

RESUMO

OBJECTIVE: Becker Muscular Dystrophy (BMD) is a neuromuscular disorder which is incurable. In this research protein interaction network of most associated proteins with BMD to provide better clarification of disorder underlying mechanism was investigated. MATERIALS & METHODS: The related genes to BMD were retrieved via string database and conducted by Cytoscape and the related algorithms. The network centrality analysis was performed based on degree, betweenness, closeness, and stress parameters. Gene ontology and clustering were performed via ClueGO analysis. RESULTS: DMD as the super-hub as well as other central proteins including UTRN, TTN, DNM2, and RYR1 are important in BMD in terms of interactive features. The impairment of muscular contraction may be vital in BMD disease pathogenesis as it is the highlighted biological process term obtained by ClueGO analysis. CONCLUSION: DMD targeting may be the main concern for dystrophy clinical approaches. However, the other suggested proteins should be evaluated. Targeting these key proteins are required for treatment goals following extensive validation studies.

12.
Eur J Pharmacol ; 853: 25-32, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876980

RESUMO

Oxidative stress plays an important role in auditory dysfunction. Exogenous cell therapy has brought new hopes for repairing mammalian inner ear hair cells. However, poor cell viability of transplanted cells under oxidative stress conditions has limited their therapeutic potential. The adipocytokine apelin-13 was isolated from a bovine stomach. Apelin-13 might protect oxidative stress-induced hair cell damage was raised considering other oxidative stress-induced injury, including brain ischemia-induced cell death. Therefore, we evaluated the protective effects of apelin- 13 on the damage induced by hydrogen peroxide (H2O2) to the hair cells-derived from bone marrow mesenchymal stem cells (BMSCs) in vitro. Stem cells were differentiated into hair cell- like cells with B27, FGF, EGF and IGF-1. Expression of neuron specific markers including ß tubulin III, Nestin, MAP2, Neurofilament 68 and GFAP was tested by flow cytometry. As well, inner ear hair cell markers such as Myosin VIIA, Sox2 and TrkB expression were assayed by immunocytochemistry (ICC) method. We designed an in vitro model of oxidative stress by exposing hair cell- like cells to H2O2. Protein expression levels of caspase-3, Bax and Bcl-2 were detected by western blot. Apoptotic cells were also detected by acridin-orange staining and TUNEL assay. Protein expression of caspase-3 and Bax/Bcl-2 ratio was significantly lower in the apelin-13-pretreated group than only H2O2 treated group. In addition, apoptotic cells were significantly decreased in the apelin-13+H2O2 co-treated cells compared to the H2O2-treated group. Treating hair cells-like cells with apelin13 increases their survival against oxidative stress damage by inhibition of apoptosis signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Células-Tronco Mesenquimais/citologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Ciliadas Auditivas/citologia , Células Ciliadas Auditivas/metabolismo , Peróxido de Hidrogênio/farmacologia , Masculino , Neurônios/citologia , Ratos , Ratos Wistar
13.
Iran J Pharm Res ; 17(1): 415-425, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755572

RESUMO

The most common malignant neoplasm of the head and neck region is laryngeal cancer which presents a significant international health problem. The present study aims to screen potential proteins related to laryngeal cancer by network analysis to further understanding disease pathogenesis and biomarker discovery. Differentially expressed proteins were extracted from literatures of laryngeal cancer that compare proteome profiling of patient>s tissue with healthy controls. The PPI network analyzed for up and down regulated proteins with Cytoscape Version 3.4. After PPI construction, topological properties of the two networks have been analyzed. Besides, by using MCODE. the Gene Ontology (GO) analysis, the related modules and pathways were examined. Our study screened 275 differentially changed proteins, including 136 up- and 139 down-regulated proteins. For each network, it has been considered 20 key proteins as hub and 20 as bottleneck. A number of 26 hub-bottleneck nodes is introduced for the two networks. A total of 11 modules including 6 downregulated and 5 upregulated network modules were obtained. The most significant GO function in the significant upregulated module was the RNA processing, and the most significant one in the downregulated module with highest score was the respiratory electron transport chain. Among 275 investigated proteins, 12 crucial proteins are determined that 4 of them can be introduce as a possible biomarker panel including YWHAZ, PPP2R1A, HSP90AA1, and CALM3 for human laryngeal cancer.

14.
Neural Regen Res ; 13(1): 154-160, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29451220

RESUMO

Previous animal studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling pathway plays an important role in the targeted migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the injured area. In the present study, we aimed to investigate the potential role of chemotactic SDF-1/CXCR4 signaling pathway in the homing of transplanted BMSCs to the injured cochlea after noise-induced hearing loss (NIHL) in a rat model. White noise exposure (110 dB) paradigm was used for hearing loss induction in male rats for 6 hours in 5 days. Distortion-product otoacoustic emission (DPOAE) responses were recorded before the experiment and post noise exposure. Hoechst 33342-labeled BMSCs and CXCR4 antagonist (AMD3100)-treated BMSCs were injected into the rat cochlea through the round window. SDF-1 protein expression in the cochlear tissue was assayed using western blot assay. The number of labeled BMSCs reaching the endolymph was determined after 24 hours. SDF-1 was significantly increased in the cochlear tissue of rats in the noise exposure group than in the control group. The number of Hoechst 33342-labeled BMSCs reaching the endolymph of the cochlea was significantly smaller in the AMD3100-treated BMSCs group than in the normal BMSCs group. Our present findings suggest that the SDF-1/CXCR4 signaling pathway has a critical role in BMSCs migration to the injured cochlea in a rat model of noise-induced hearing loss.

15.
Addict Health ; 10(1): 64-66, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627386
16.
J Lasers Med Sci ; 8(3): 143-149, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29123635

RESUMO

Introduction: Periodontitis is a set of inflammatory disorders characterized by periodontal attachment loss and alveolar bone resorption. Because of deficiency in periodontitis mechanical therapy, this study was aimed to explore the molecular influence of the erbiumdoped: yttrium aluminum garnet (Er:YAG) laser and cyclosporin A (CsA) on human gingival fibroblasts (HGFs) for improvement in periodontal diseases therapy. Methods: We focused on articles that studied the proteome profiles of HGFs after treatment with laser irradiation and application of CsA. The topological features of differentially expressed proteins were analyzed using Cytoscape Version 3.4.0 followed by module selection from the protein-protein interaction (PPI) network using Cluster ONE plugin. In addition, we performed gene ontology (GO) enrichment analysis for the densely connected region and key proteins in both PPI networks. Results: Analysis of PPI network of Er:YAG laser irradiation on HGFs lead to introducing YWHAZ, VCP, HNRNPU, YWHAE, UBA52, CLTC, FUS and IGHG1 as key proteins while similar analysis revealed that ACAT1, CTSD, ALDOA, ANXA2, PRDX1, LGALS3, ARHGDI and EEF1A1 are the crucial proteins related to the effect of drug. GO enrichment analysis of hubbottleneck proteins of the 2 networks showed the different significant biological processes and cellular components. The functional enrichments of module of Er:YAG laser network are included as fatty acid transmembrane transport, cytokinesis, regulation of RNA splicing and asymmetric protein localization. There are not any significant clusters in network of HGF treated by CsA. Conclusion: The results indicate that there are 2 separate biomarker panels for the 2 treatment methods.

17.
J Lasers Med Sci ; 8(Suppl 1): S20-S21, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29071030

RESUMO

Introduction: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes which can cause vision loss or blindness ultimately. Non enzymatic glycation of proteins leads to advanced glycation end products (AGEs) in DR. Since laser therapy is a well-established method, in this study, protein-protein interaction (PPI) network is applied for protein targets in DR disease in rats treated by laser. Methods: In this study, we focused on articles that investigated and compared the proteome profiles of DR rats with healthy control and also DR rats before and after laser therapy. The networks of related differentially expressed proteins were explored using Cytoscape version 3.3.0, the PPI analysis methods and ClueGO. Results: Analysis of PPI network of 37 related proteins to DR rats including 108 nodes, introduced 10 hub-bottleneck proteins and 5 concerned biochemical pathways. On the other hand, PPI analysis of related proteins to DR rats before and after laser therapy corresponded to 33 proteins and 2 biological pathways. Discussion: Centrality and cluster screening identified hub-bottelneck genes, including Aldoa, HSPD1, Pgam2, Mapk3, SLC2A4, Ctnnb1, Ywhab, HSPA8, GAPDH and Actb for DR rats versus healthy control and ENO1, Aldoa, GAPDH for DR samples after laser therapy. CONCLUSION: Gene expression analysis of the DR samples treated via laser therapy provides a molecular evidence in support of the therapeutic effect of laser.

18.
Behav Brain Res ; 324: 71-76, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28212940

RESUMO

Many studies have been shown that maternal stress during pregnancy and in early life period influences offspring in the behavioral and molecular aspects in human and animal models. Recent research has indicated that the environmental condition of males before conception has effects on next generations. We evaluated whether preconception paternal stress (PPS) could influence on hippocampal glucocorticoid receptor gene (GR), (NR3C1) expression, corticosterone response and behavioral outcomes of their offspring. For this purpose, adult male rats were subjected to daily 10min session of forced swimming for 21 consecutive days. Then, two parental breeding groups were formed: stressed father (SF) and non-stressed father (NSF) or control group. 30-day-old pups were tested for anxiety-like behavior by using the elevated plus maze (EPM). Serum corticosterone level was also measured by ELISA. Hippocampal NR3C1 DNA methylation, gene and protein expression were respectively assayed by methylation sensitive restriction enzymes (Real Time PCR), Reverse Transcriptase PCR (RT-PCR) and Western-blotting in all groups. More anxiety-related behavior, serum corticosterone concentration, DNA methylation levels of NR3C1 and lower expression of this gene were significantly observed in paternally stressed pups compared to control pups. As well, molecular changes were more pronounced in male pups compared to female pups. Our results revealed that paternal stress prior to conception has a negative effect on molecular, hormonal and behavioral outcomes in their offspring.


Assuntos
Metilação de DNA , Hipocampo/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores de Glucocorticoides/metabolismo , Estresse Psicológico/metabolismo , Animais , Ansiedade/metabolismo , Corticosterona/sangue , Epigênese Genética , Feminino , Masculino , Gravidez , RNA Mensageiro/metabolismo , Ratos Wistar
19.
Mol Neurobiol ; 54(8): 6436-6445, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27726112

RESUMO

Environmental factors, especially stress, can remain pervasive effects across the lifespan. Traumatic experiences are risk factors for the behavioral and emotional disorders. Since brain-derived neurotrophic factor (BDNF) is the important regulator of neural survival, development, and its genetic and epigenetic alterations which have been linked with several neuropsychiatric disorders, the present study investigated the effect of maternal adulthood stress on molecular changes of BDNF and tyrosine kinase-coupled receptor (TrkB) in the hippocampus of 30-day-old offspring. To induce stress, we employed a repeated forced swimming model for female rats across 21 days. Then, they were divided into two parental breeding groups: stressed mother (SM) and non-stressed mother (NSM) or control group. Anxiety-like behavior was tested in adult female rats and 30-day-old pups by using the elevated plus maze (EPM). The level of serum corticosterone was also measured by ELISA. BDNF and TrkB gene methylation and protein expression in the hippocampus were detected using real-time PCR and Western blotting in all groups. Thirty-day-old male and female pups from SM groups had a significantly more serum corticosterone concentration, DNA methylation levels of BDNF and TrKB, and lower expression of these genes compared to pups from the control groups. Also, male pups from stressed mother exhibited significant anxiety-like behavior compared to male pups from the control mothers. These findings suggest that molecular changes formed by maternal stress experience even before conception persist to the next generation and will negatively influence on phenotypes of offspring.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transdução de Sinais/fisiologia , Estresse Psicológico/metabolismo , Animais , Ansiedade/metabolismo , Corticosterona/sangue , Metilação de DNA , Feminino , Masculino , Aprendizagem em Labirinto/fisiologia , Gravidez , Ratos , Ratos Wistar , Receptor trkB/metabolismo
20.
Medicine (Baltimore) ; 95(19): e3656, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27175693

RESUMO

The incidence of smuggling and transporting illegal substances by internal concealment, also known as body packing, is on the rise. The clinical approach to such patients has been changed significantly over the past 2 decades. However, despite a recorded increase in body packing in general, there are controversies in the management of these patients. We aimed to gather data regarding the demographic characteristics, treatment, and outcome of body packers, which were that referred to Loghman Hakim Hospital, Tehran, Iran.The data of all body packers admitted to Loghman Hakim Hospital during 2010 to 2014 were evaluated retrospectively. Data regarding the demographic characteristics of the patients, findings of clinical imaging, treatment, and outcome were recorded.In this study, 175 individuals with a mean age of 31 ±â€Š10 years were assessed. The most common concealed substances were crack (37%), crystal (17%), opium (13%), and heroin (6%). According to the results of surgery and imaging (abdominal radiography or computed tomography), the most common place for concealment was stomach in 33.3% and 12% of cases, respectively. Imaging findings were normal in 18% of the individuals. Forty-eight (27%) patients underwent surgery. The main indications for surgery were clinical manifestations of toxicity (79%) and obstruction of the gastro-intestinal tract (17%). The most common surgical techniques were laparotomy and gastrotomy (50%). The mean duration of hospitalization was 3.8 ±â€Š4 days. The mortality rate was 3%.Conservative treatment of body packers seems to be the best treatment method. Careful monitoring of the patients for possible signs and symptoms of intoxication and gastro-intestinal obstruction is strongly recommended.


Assuntos
Gerenciamento Clínico , Tráfico de Drogas , Corpos Estranhos/epidemiologia , Drogas Ilícitas , Estômago/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Corpos Estranhos/etiologia , Corpos Estranhos/terapia , Trato Gastrointestinal/cirurgia , Hospitalização/estatística & dados numéricos , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos Retrospectivos , Adulto Jovem
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