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Natural polyphenols have been found to have some protective effects against neurodegenerative and neurodevelopmental disorders, which are attributed to a variety of biological properties, particularly antioxidant, immunomodulatory, and anti-inflammatory effects. Autism spectrum disorder is a complex neurological and neurodevelopmental disorder with no currently effective clinical treatment for its core symptoms. Regarding the management of autism spectrum disorder core symptoms, a number of experimental and clinical studies have been made using well-known dietary polyphenols with different effects and molecular mechanisms. The aim of this paper is to present the most effective natural polyphenols with the relevant molecular mechanisms in preclinical and clinical autism spectrum disorder studies.
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Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Humanos , Polifenóis/uso terapêutico , Transtorno do Espectro Autista/tratamento farmacológico , Antioxidantes/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory and wound-healing potential of Feijoa sellowiana fruit extract using stereological and molecular methods in experimental rat models. MATERIALS: Male Wistar rats were divided into four equal groups: non-treated, vehicle, Feijoa sellowiana fruit extract ointment (5% weight/weight) and the reference drug (madecassol). All animals were treated topically once per day. At the end of the study, wound samples were harvested for histological, stereological, immunohistochemical and molecular assessments to determine the in vivo healing potential and anti-inflammatory activity. A high-performance liquid chromatography (HPLC) analysis was performed for the characterisation of the phenolic acids in the extract. RESULTS: The study included 64 rats in total. Our results showed that the wound closure, volume of new epidermis and dermis, density of fibroblasts and blood vessels, and the deposition of collagen were significantly higher in both extract and madecassol groups compared to the non-treated and vehicle groups, with superior healing in the extract group. The transcript for the transforming growth factor (TGF)-ß gene was significantly upregulated in both extract and madecassol groups compared to non-treated and vehicle groups and was highest for the extract group. The density of inflammatory cells and expression levels of the cyclooxygenase (COX)-2 protein and tumour necrosis factor (TNF)-α gene in the extract and madecassol groups, especially in the extract group, were significantly reduced compared to non-treated and vehicle groups. CONCLUSION: Our results confirm that the Feijoa sellowiana fruit extract is a valuable source of antioxidant and anti-inflammatory activities and can allow for damaged tissue in wounds to recover markedly.
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Feijoa , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Feijoa/química , Frutas/química , Masculino , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , CicatrizaçãoRESUMO
Epigallocatechin gallate is the most abundant composition of the tea catechins and is thought to be responsible for the majority of biological activity of green tea extracts such as antioxidant, anti-inflammatory, and antiapoptotic effects. Meanwhile, EGCG has been shown to be some of the neuroprotective effects against neural injuries and neurodegenerative diseases. This paper summarizes current knowledge on neuroprotective effects of EGCG and their molecular mechanisms responsible for the neuroprotection in various models of neurodegenerative and neural injury.
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Lesões Encefálicas/metabolismo , Catequina/análogos & derivados , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Extratos Vegetais/administração & dosagem , Traumatismos da Medula Espinal/metabolismo , Chá , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Lesões Encefálicas/prevenção & controle , Catequina/administração & dosagem , Catequina/metabolismo , Ensaios Clínicos como Assunto , Humanos , Doenças Neurodegenerativas/prevenção & controle , Neurônios/metabolismo , Traumatismos da Medula Espinal/prevenção & controleRESUMO
Objectives: Recent studies revealed the neuroprotective effects of epigallocatechin-3-gallate (EGCG) on a variety of neural injury models. The purpose of this study was to determine the neuroprotective effects of EGCG following sciatic nerve transection (SNT). Methods: Rats were randomly divided into four groups each as follows: Sham-operated group, SNT group, and Pre-EGCG (50-mg/kg, i.p., 30 minutes before nerve transection and followed for 3 days) and Post-EGCG (50-mg/kg, i.p., 1 hour after nerve transection and followed for 3 days) groups. Spinal cord segments of the sciatic nerve and related dorsal root ganglions were removed four weeks after nerve transection for the assessment of malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, immunohistochemistry of caspase-3, cyclooxygenase-2 (COX-2), S100beta (S100B), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Results: MDA levels were significantly decreased, and SOD and CAT activities were significantly increased in EGCG-treated rats after nerve transection. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the EGCG-treated rats after nerve transection. Also, EGCG significantly increased S100B expression. Discussion: We propose that EGCG may be effective in the protection of neuronal cells against retrograde apoptosis and may enhance neuronal survival time following nerve transection.
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Apoptose/efeitos dos fármacos , Catequina/análogos & derivados , Fármacos Neuroprotetores/administração & dosagem , Traumatismos dos Nervos Periféricos/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Animais , Catalase/metabolismo , Catequina/administração & dosagem , Masculino , Malondialdeído/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Traumatismos dos Nervos Periféricos/patologia , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: There is accumulating evidence that Juglans regia L. (GRL) leaf extract has hypoglycemic and antioxidative properties. The present study aimed to investigate the protective effects of GRL leaf extract against diabetic nephropathy (DN). METHODS: In total, 28 male adult Sprague-Dawley rats were used. The DN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats received intragastric administration of GRL leaf extract (200 mg/kg/day) starting 1 week (preventive group) and 4 weeks (curative group) after the onset of hyperglycemia up to the end of the 8th week, whereas other diabetic rats received only isotonic saline (diabetic group) as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic nephropathy, various parameters of apoptosis and inflammation were assessed. Statistical analysis was performed using the SPSS software, version 15.0. The data were compared between the groups using the Tukey's multiple comparison test and the analysis of the variance. P values Ë0.05 were considered statistically significant. RESULTS: Fasting blood sugar (FBS) levels (P=0.001) and histopathological changes in the kidney of diabetic rats attenuated after GRL leaf extract consumption. Greater caspase-3 (P=0.004), COX-2 (P=0.008), PARP (P=0.007), and iNOS (P=0.005) expression could be detected in the STZ-diabetic rats, which were significantly (P=0.009) attenuated after GRL leaf extract consumption. In addition, attenuation of lipid peroxidation in the diabetic rats was detected after GRL consumption (P=0.01). CONCLUSION: GRL leaf extract exerts preventive and curative effects against diabetic nephropathy.
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BACKGROUND: Recent studies shows that hyperbaric oxygen (HBO) therapy exerts some protective effects against neural injuries. The purpose of this study was to determine the neuroprotective effects of HBO following sciatic nerve transection (SNT). METHODS: Rats were randomly divided into five groups (n = 14 per group): Sham-operated (SH) group, SH + HBO group, SNT group, and SNT + pre- and SNT + post-HBO groups (100% oxygen at 2.0 atm absolute, 60 min/day for five consecutive days beginning on 1 day before and immediately after nerve transaction, respectively). Spinal cord segments of the sciatic nerve and related dorsal root ganglions (DRGs) were removed 4 weeks after nerve transection for biochemical assessment of malodialdehyde (MDA) levels in spinal cord, biochemical assessment of superoxide dismutase (SOD) and catalse (CAT) activities in spinal cord, immunohistochemistry of caspase-3, cyclooxigenase-2 (COX-2), S100beta (S100ß), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in spinal cord and DRG. RESULTS: The results revealed that MDA levels were significantly decreased in the SNT + pre-HBO group, while SOD and CAT activities were significantly increased in SNT + pre- and SNT + post-HBO treated rats. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the HBO-treated rats after nerve transection. Also, HBO significantly increased S100ß expression. CONCLUSIONS: Based on these results, we can conclude that pre- and post-HBO therapy had neuroprotective effects against sciatic nerve transection-induced degeneration.
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Oxigenoterapia Hiperbárica/métodos , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Nervo Isquiático/patologia , Animais , Caspase 3/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismoRESUMO
BACKGROUND: Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. METHODS: The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. RESULTS: Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. CONCLUSION: Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against neuropathy.
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Antioxidantes/farmacologia , Neuropatias Diabéticas/metabolismo , Juglans/química , Nervos Periféricos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Neuropatias Diabéticas/induzido quimicamente , Hipoglicemiantes/farmacologia , Masculino , Nervos Periféricos/patologia , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Estreptozocina/efeitos adversosRESUMO
BACKGROUND: Deltamethrin (DM) is a synthetic pyrethroid insecticide which can lead to pathological effects in mammals through oxidative stress. On the other hand, virgin olive oil (VOO) is a rich source of phenolic compounds with antioxidants. The aim of the present study was to determine the protective effects of VOO against DM-induced hepatotoxicity. METHODS: Thirty-six mice were randomly separated into 4 groups: vehicle group, VOO group, DM group, and DM plus VOO group. Immunohistochemistry of PARP, COX-2, and caspase-3 with the biochemical analysis of malondialdehyde and total antioxidant capacity levels were performed in the liver samples 5 weeks after gavaging. Statistical analysis was performed using SPSS, version 15. The data were compared between the groups using the Tukey multiple comparison tests and the analysis of the variance. A P value <0.05 was considered significant. RESULTS: The malondialdehyde level in the liver was increased in the DM group (71.18±0.01), whereas it was significantly (P=0.001) decreased after VOO administration in the DM plus VOO group (39.59±2.43). While the total antioxidant capacity level in the liver was decreased in the DM group (3.05±0.05), it was significantly increased (P=0.03) after VOO administration in the DM plus VOO group (3.95±0.04). A greater expression of caspase-3 (P=0.008), COX-2 (P =0.004), and PARP (P 0.006) could be detected in the DM group, while it was significantly (P=0.009) attenuated in the DM plus VOO group. Also, the degeneration of hepatocytes, which was detected in the DM group, was attenuated after VOO consumption. CONCLUSIONS: VOO exerted protective effects against DM-induced hepatotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and antioxidative properties.
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Successful treatment of diabetic wounds requires multifactorial approaches. Herein we investigated the effects of a bioengineered three-dimensional dermal derived matrix-scaffold (DMS) in combination with hyperbaric oxygen (HBO) in repairing of wound model in diabetic rats. Thirty days after induction of diabetes, a circular wound was created and treatments were performed for 21 days. Animals were randomly allocated into the untreated group, DMS group, HBO group, and DMS+HBO group. On days 7, 14, and 21, tissue samples were obtained for stereological, molecular, and tensiometrical assessments. Our results showed that the wound closure rate, volume of new dermis and epidermis, numerical density fibroblasts and blood vessels, collagen density, and biomechanical characterize were significantly higher in the treatment groups than in the untreated group, and these changes were more obvious in the DMS+HBO ones. Moreover, the expression of TGF-ß, bFGF, miRNA-21, miRNA-146a, and VEGF genes were meaningfully upregulated in treatment groups compared to the untreated group and were greater in the DMS+HBO group. This is while expression of TNF-α and IL-1ß, as well as the numerical density of neutrophil and macrophage decreased more considerably in the DMS+HBO group than in the other groups. Overall, using both DMS engraftment and HBO treatment has more effects on diabetic wound healing.
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Diabetes Mellitus Experimental , Oxigenoterapia Hiperbárica , Alicerces Teciduais , Cicatrização , Animais , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/patologia , Ratos , Alicerces Teciduais/química , Masculino , Ratos Sprague-DawleyRESUMO
Olive oil is a rich source of phenolic components which have a wide variety of beneficial health effects in vitro, in vivo, and clinically. The beneficial effects of olive oil phenols attributed to a variety of biological activities including free radical scavenging/antioxidant actions, anti-inflammatory effects, anti-carcinogenic properties, and anti-microbial activities. On the other hand, olive oil phenols have been shown to be some of neuroprotective effects against cerebral ischemia, spinal cord injury, Huntington's disease, Alzheimer's diseases, multiple sclerosis, Parkinson's disease, aging, and peripheral neuropathy. This paper summarizes current knowledge on the mechanisms of neuroprotective effects of olive oil phenols.
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Frutas/química , Alimento Funcional , Fármacos Neuroprotetores/uso terapêutico , Olea/química , Fenóis/uso terapêutico , Óleos de Plantas/uso terapêutico , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/uso terapêutico , Antioxidantes/análise , Antioxidantes/uso terapêutico , Apoptose , Dieta Mediterrânea , Alimento Funcional/análise , Humanos , Fármacos Neuroprotetores/análise , Azeite de Oliva , Fenóis/análise , Óleos de Plantas/químicaRESUMO
Recent evidence suggests that stem cell therapy has beneficial effects on nerve damage. These beneficial effects were subsequently found to be exerted in part in a paracrine manner by the release of extracellular vesicles. Stem cell-secreted extracellular vesicles have shown great potential to reduce inflammation and apoptosis, optimize the function of Schwann cells, regulate genes related to regeneration, and improve behavioral performance after nerve damage. This review summarizes the current knowledge on the effect of stem cell-derived extracellular vesicles on neuroprotection and regeneration along with their molecular mechanisms after nerve damage.
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The most important factors in the non-optimal healing of diabetic wounds are the lack of a suitable scaffold in the wound site for the migration and replacement of cells, as well as the lack of blood supply and effective growth factors in the wound site. Herein we investigated whether a bioengineered micro-porous three-dimensional decellularized amniotic membrane-scaffold (DAMS) in combination with adipose-derived stem cells (ASCs) could promote healing in ischemic wounds in diabetic type 1 rat. The diabetic animals were randomly divided into non-treated (untreated group), engraftment by DAMS (DAMS group), transplanted by ASCs (ASC group), and DAMS in combination with ASCs (DAMS+ASC group). Stereological, immunohistochemical, molecular, and tensiometrical assessments were performed on post-surgical days 7, 14, and 21. We found that the rate of wound closure, the volumes of new epidermis and dermis, the numerical density of fibroblasts and blood vessels, the numbers of proliferating cells and collagen deposition as well as biomechanical properties of the healed wounds were significantly higher in the treatment groups in comparison to the untreated group, and were the highest in DAMS+ASC ones. The transcripts for TGF-ß and VEGF genes were significantly upregulated in all treatment regimens compared to the untreated group and were the highest for DAMS+ASC group. This is while expression of TNF-α and IL-1ß as well as cell density of neutrophils decreased more significantly in DAMS+ASC group as compared with other groups. Overall, it was found that using both DAMS engraftment and ASC transplantation has more impact on diabetic wound healing.
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Tecido Adiposo , Diabetes Mellitus , Ratos , Animais , Âmnio , Cicatrização , Células-TroncoRESUMO
Spinal cord ischemia-reperfusion injury (IR) is a terrible non-traumatic injury that occurs after abdominal aortic occlusion and causes serious damage to neurological function. Several treatment strategies have been suggested for IR, but they were not unable to effectively improve these conditions. Herein we investigated whether exosomes derived from human placental mesenchymal stem cells (hpMSCs-Exos) in combination with hyperbaric oxygen (HBO) could alleviate injury and promote recovery in IR rats. Eighty male Sprague-Dawley rats were randomly allocated into five equal groups. In addition to the control group that only underwent laparotomy, IR animals were planned into four groups as follows: IR group; IR-Exos group; IR-HBO group; and IR-Exos + HBO group. Neurological function evaluated before, 6 h, 12 h, 24 h, and 48 h after injury. After the last neurological evaluation, tissue samples were obtained for stereological, biochemical, and molecular assessments. Our results indicated that the neurological function scores (MDI), the numerical density of neurons, the levels of antioxidative factors (GSH, SOD, and CAT), and anti-inflammatory cytokine (IL-10) were considerably greater in treatment groups than in the IR group, and these changes were more obvious in the IR-Exos + HBO ones. This is while the numerical density of glial cells, the levels of an oxidative factor (MDA) and inflammatory cytokines (IL-1ß, TNF-α, and IL-18), as well as the expression of an apoptotic protein (caspase-3) were meaningfully decreased in treatment groups, especially IR-Exos + HBO group, compared to the IR group. Generally, it was found that co-administration of hpMSCs-Exos and HBO has synergistic neuroprotective effects in the rats undergoing IR.
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The occurrence of wounds and defects in the healing process is one of the main challenges in diabetic patients. Herein, we investigated whether adipose-derived stem cells (ADSCs)-derived exosomes loaded bioengineered micro-porous three-dimensional amniotic membrane-scaffold (AMS) could promote healing in diabetic rats. Sixty diabetic rats were randomly allocated into the control group, exosome group, AMS group, and AMS + Exo group. On days 7, 14, and 21, five rats from each group were sampled for stereological, immunohistochemical, molecular, and tensiometrical assessments. Our results indicated that the wound closure rate, the total volumes of newly formed epidermis and dermis, the numerical densities of fibroblasts and proliferating cells, the length density blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably greater in the treated groups than in the control group, and these changes were more obvious in the AMS + Exo ones. Furthermore, the expression of TGF-ß, bFGF, and VEGF genes was meaningfully upregulated in all treated groups compared to the control group and were greater in the AMS + Exo group. This is while expression of TNF-α and IL-1ß, as well as cell numerical densities of neutrophils, M1 macrophages, and mast cells decreased more considerably in the AMS + Exo group in comparison with the other groups. Generally, it was found that using both AMS transplantation and ADSCs-derived exosomes has more effect on diabetic wound healing.
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Diabetes Mellitus Experimental , Exossomos , Células-Tronco Mesenquimais , Humanos , Ratos , Animais , Diabetes Mellitus Experimental/terapia , Âmnio , Cicatrização , Fatores Imunológicos , ObesidadeRESUMO
OBJECTIVE: Recent studies revealed the neuroprotective effects of hyperbaric oxygen (HBO) on spinal cord injury (SCI). Meanwhile, the use of methylprednisolone (MP) is one of the current protocols with limited effects in SCI patients. Accordingly, the aim of the present study was to investigate the effect of combined HBO and MP treatment on SCI. DESIGN: The present study was conducted on five groups of rats each as follows: Sham group (underwent laminectomy alone at T9 level vertebra); SCI group (underwent moderate contusive SCI); MP group (underwent SCI and received MP); HBO group (underwent SCI and received HBO); HBO + MP group (underwent SCI and simultaneously received MP and HBO). Blood serum and Spinal cord tissue samples were taken 48 h after SCI for analysis of serum ferric reducing antioxidant power (FRAP) and tissue malodialdehyde (MDA) levels as well as immunohistochemistry of caspase-3 and tumor necrosis factor-alpha (TNF-α). Neurological function was evaluated by the Basso-Beattie-Bresnehan (BBB) locomotion scores until the end of experiments. Additionally, histopathology was assessed at the end of the study. SETTING: Mazandaran University of Medical Sciences, Sari, Iran. RESULTS: Combination therapy with HBO and MP in the HBO + MP group significantly decreased MDA as well as increased FRAP levels compared to other treatment groups. Meanwhile, attenuated TNF-α and Caspase-3 expression could be significantly detected in the HBO + MP group. At the end of treatment, the neurological outcome was significantly improved and the extent of injured spinal tissue was also significantly reduced in the HBO + MP compared to other treatment groups. CONCLUSION: The results suggest that combined therapy with MP and HBO has synergistic effects on SCI treatment.
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Oxigenoterapia Hiperbárica , Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Ratos , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Caspase 3/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Oxigenoterapia Hiperbárica/métodos , Metilprednisolona/farmacologia , Metilprednisolona/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , Medula Espinal/patologia , OxigênioRESUMO
BACKGROUND: Diabetic wounds are one of the most important issues in diabetic patients. It seems that Juglans regia L. leaf with antioxidant and anti-inflammatory potentials can be profitable for healing of diabetic wounds. The aim of present study was to investigate the topical administration of Juglans regia L. leaf extract in diabetic wound healing. METHODS: Seventy-five diabetic male rats were randomly divided into 5 groups (n = 15), including: untreated (Control) group, Eucerin group, 2% Juglans regia L. ointment (JRL 2%) group, 5% Juglans regia L. ointment (JRL 5%) group, and Phenytoin group as a reference drug. Sampling was performed at days 7, 14, and 21 after surgery. Evaluation tests included stereology, immunohistochemistry, molecular, and biomechanical. RESULTS: Our results showed that the wound closure rate, volumes of newly formed of epidermis and dermis, density of fibroblasts and blood vessels, collagen deposition, density of proliferation cells, expression levels of TGF-ß and VEGF genes, and biomechanical characteristics were significantly higher in extract groups compared to control and eucerin groups, however, these changes were considerable in the JRL 5% group (P < 0.05). This is while that the density of neutrophils and expression levels of TNF-α and IL-1ß genes in the extract groups, especially in the JRL 5% group, were significantly reduced compared to control and eucerin groups (P < 0.05). CONCLUSION: Topical administration of Juglans regia L. leaf extract, especially in 5% concentration, considerably accelerates diabetic wound healing.
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Diabetes Mellitus , Juglans , Administração Tópica , Animais , Antioxidantes , Colágeno , Diabetes Mellitus/tratamento farmacológico , Juglans/química , Juglans/metabolismo , Masculino , Pomadas , Fenitoína , Extratos Vegetais/química , Ratos , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio Vascular , CicatrizaçãoRESUMO
Based on its multifactorial nature, successful treatment of diabetic wounds requires combinatorial approach. In this regard, we hypothesized that engraftment of a bioengineered micro-porous three-dimensional human amniotic membrane-scaffold (HAMS) loaded by SDF-1α (SHAMS) in combination with hyperbaric oxygen (HBO), throughout mobilization and recruitment of endothelial progenitor cells (EPCs), could accelerate wound healing in rats with type 1 diabetes mellitus. To test this hypothesis, 30 days after inducting diabetes, an ischemic wound was created in rat skin and treatments were performed for 21 days. In addition to wounded non-diabetic (ND) group, diabetic animals were randomly divided into non-treated (NT-D), HBO-treated (HBO-D), HBO-treated plus HAMS transplantation (HBO+HAMS-D) or HBO-treated in combination with SHAMS transplantation (HBO+SHAMS-D) groups. Our results on post-wounding days 7, 14 and 21 showed that the wound closure, volume of new dermis and epidermis, numerical density of basal cells of epidermis, fibroblasts and blood vessels, number of proliferating cells, deposition of collagen and biomechanical properties of healed wound were considerably higher in both HBO+HAMS-D and HBO+SHAMS-D groups in comparison to those of the NT-D and HBO-D groups, and were the highest in HBO+SHAMS-D ones. The transcripts for Vegf, bFgf, and Tgf-ß genes were significantly upregulated in all treatment regimens compared to NT-D group and were the highest for HBO+SHAMS-D group. This is while expression of Tnf-α and Il-1ß as well as cell density of neutrophil and macrophage decreased more significantly in HBO+SHAMS-D group as compared with NT-D or HBO-D groups. Overall, it was found that using both HAMS transplantation and HBO treatment has more impact on diabetic wound healing. Moreover, SDF-1α loading on HAMS could transiently improve the wound healing process, as compared with the HBO+HAMS-D group on day 7 only.
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Diabetes Mellitus Experimental , Oxigenoterapia Hiperbárica , Animais , Humanos , Ratos , Âmnio/metabolismo , Quimiocina CXCL12/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Oxigênio , CicatrizaçãoRESUMO
Recent evidence suggests that stem cell therapy has beneficial effects on spinal cord injury. It was subsequently established that these beneficial effects may be mediated through release of paracrine factors, a kind of extracellular vesicle known as exosomes. Stem cell-secreted nano-sized exosomes have shown great potential to reduce apoptosis and inflammation, enhance angiogenesis, and improve functional behavioral recovery following spinal cord injury. This review summarizes current knowledge about the influence of exosomes derived from stem cells on spinal cord protection and regeneration with their molecular mechanisms after injury.
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Exossomos , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Células-Tronco/metabolismo , Animais , Exossomos/metabolismo , Exossomos/transplante , Humanos , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapiaRESUMO
Hyperbaric oxygen therapy, intermittent breathing of 100% oxygen at a pressure upper than sea level, has been shown to be some of the neuroprotective effects and used therapeutically in a wide range of neurological disorders. This review summarizes current knowledge about the neuroprotective effects of hyperbaric oxygen therapy with their molecular mechanisms in different models of neurological disorders.
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Oxigenoterapia Hiperbárica , Fármacos Neuroprotetores , Fármacos Neuroprotetores/uso terapêutico , OxigênioRESUMO
Objective: Paraplegia or paraparesis due to spinal cord ischemia is one of the complications following thoracoabdominal aortic surgery. Recent studies revealed the neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) on a variety of neurological disorders. The purpose of this study was to determine the neuroprotective effects of EGCG following spinal cord ischemia-reperfusion injury (IRI).Design: The present study was conducted on four groups of rats each as follows: Sham-operated group (laparotomy alone); Control group (with IRI); EGCGI group (50-mg/kg, i.p., before IRI), and EGCGII group (50-mg/kg, i.p., after IRI). Neurological function evaluated with motor deficit index (MDI) test. Spinal cord samples were taken 48â h after IRI and studied for determination of malodialdehyde (MDA) level, histopathology, and immunohistochemistry of caspase-3, TNF-α, and iNOS.Setting: Mazandaran University of Medical Sciences, Sari, Iran.Results: The level of MDA was significantly decreased in EGCG-treated rats. Attenuated caspase-3, TNF-α, and iNOS expression could be significantly detected in the EGCG-treated rats. Also, EGCG reduced the extent of degeneration of the spinal cord neurons, in addition to a significant reduction of MDI.Conclusion: The results suggest that pre- and post-treatment with EGCG may be effective in protecting spinal cord from IRI.