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Spermatogonia stem cells (SSCs) are a unique cell population maintaining male spermatogenesis during life, through their potential for proliferation and differentiation. The application of silicon nanoparticles (SNs) and hyaluronic acid (HA) to induce the differentiation of SSCs seems promising. Herein, we investigate the effect of SN and HA scaffolds on the progression of SSCs spermatogenesis in mice. Initially SSCs were isolated from healthy immature mice and cultured on prepared scaffolds (HA, SN, and HA/SN) in a 3D culture system. Then viability of SSCs cultured on scaffolds was examined using MTT assay and Acridine Orange staining. Then SSCs cultured on scaffolds were transplanted into epididymal adipose tissue (EAT) in mature mice and the result was studied by H&E and IHC staining 8 weeks after transplantation. MTT and Acridine Orange analysis revealed that among three different scaffolds HA/SN based scaffold causes considerable toxicity on SSCs (P < 0.05) while H&E staining showed that culture of SSCs on HA, SN, and HA/SN scaffolds has a positive effect on the progression of SSCs spermatogenesis after transplantation into EAT. IHC staining identified TP1, TEKT1, and PLZF as crucial biomarkers in the spermatogenesis development of SSCs transplanted to EAT. According to the presence of these biomarkers in different experimental groups, we found the most spermatogenesis development in SSCs cultured on HA/SN scaffold (PLZF, P < 0.01) (TEKT1, P < 0.01) (TP1, P < 0.001). Our study showed that, although the cytotoxic effect of the HA/SN scaffold decreases the viability rate of SSCs; however, SSCs that survive on HA/SN scaffold showed more ability to progress in spermatogenesis after transplantation into EAT.
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Ácido Hialurónico , Espermatogonias , Ratones , Animales , Masculino , Espermatogonias/trasplante , Silicio , Naranja de Acridina , Biomarcadores , Células Madre , Proliferación Celular , TestículoRESUMEN
BACKGROUND: Pain is an uncomfortable sensation in the body. Kaempferol is a flavonoid with antinociceptive effects. Transient receptor potential (TRP) channels have been characterized in the sensory system. OBJECTIVE: This study evaluated the central antinociceptive effect of Kaempferol and possible mechanisms of action of transient receptor potential cation channel subfamily V member 1 (TRPV1). METHODS: Capsaicin as a TRPV agonist (5 µg/µL, intracerebroventricular [ICV]) and capsazepine as its antagonist (10 µg/µL, icv) were used to test the analgesic effect of kaempferol (1.5 mg, ICV). Morphine (10 µg, ICV) was used as a positive control. The other groups were treated with a combination of kaempferol and capsaicin, kaempferol and capsazepine, and capsaicin and capsazepine. The cannula was implanted in the cerebroventricular area. The tail-flick, acetic acid, and formalin tests were used to assess analgesic activity. For evaluation of antiinflammatory effect, the formalin-induced rat paw edema was used. RESULTS: Kaempferol significantly decreased pain in the acute pain models, including the tail-flick and the first phase of the formalin test. In the late phase of the formalin test, as a valid model of nociception, capsazepine inhibited the antinociceptive effect of kaempferol. CONCLUSIONS: Kaempferol has an analgesic effect in the acute pain model and can affect inflammatory pain. Also, the TRPV1 channel plays a role in the antinociceptive activity of kaempferol.
ANTECEDENTES: A dor é uma sensação desconfortável no corpo. Kaempferol é um flavonoide com efeitos antinociceptivos. Canais receptores de potencial transitório têm sido caracterizados no sistema sensorial. OBJETIVO: Este estudo avaliou o efeito antinociceptivo central do kaempferol e os possíveis mecanismos de ação do TRPV1. MéTODOS: Capsaicina como agonista de TRPV (5 µg/µL, intracerebroventricular [ICV]) e capsazepina como seu antagonista (10 µg/µL, icv) foram usados para testar o efeito analgésico do kaempferol (1,5 mg, ICV). A morfina (10 µg, ICV) foi usada como controle positivo. Os outros grupos foram tratados com uma combinação de kaempferol e capsaicina, kaempferol e capsazepina e capsaicina e capsazepina. A cânula foi implantada na área cerebroventricular. Os testes de movimento de cauda, ácido acético e formalina foram usados para avaliar a atividade analgésica. Para avaliação do efeito anti-inflamatório, foi utilizado o edema de pata de rato induzido por formalina. RESULTADOS: Kaempferol diminuiu significativamente a dor nos modelos de dor aguda, incluindo o movimento da cauda e a primeira fase do teste de formalina. Na fase tardia do teste da formalina, como modelo válido de nocicepção, a capsazepina inibiu o efeito antinociceptivo do kaempferol. CONCLUSõES: Kaempferol tem efeito analgésico no modelo de dor aguda e pode afetar a dor inflamatória. Além disso, o canal TRPV1 desempenha um papel na atividade antinociceptiva do kaempferol.
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Dolor Agudo , Canales de Potencial de Receptor Transitorio , Ratas , Animales , Capsaicina/farmacología , Quempferoles/farmacología , Flavonoides , Canales Catiónicos TRPV/agonistas , Analgésicos/farmacología , AntiinflamatoriosRESUMEN
OBJECTIVES: This study aimed to explore the effect of concomitant use of Furosemide (FRS) and Valproic acid (VPA), demonstrating anti-inflammation efficacy, on epilepsy, and its underlying mechanism. METHODS: Twenty-five adult male Wistar rats were divided into five groups including, Group 1: (Normal) rats received no drugs, Group 2: (E): rats were administered with a single dose of kainic acid (stereotaxic surgery), Group 3: (E + VPA): rats received Valproic acid (200 mg/kg/day/orally), Group 4: (E + FRS): rats received a single dose of Furosemide (100 mg/kg/I.P.) 30 min before epilepsy induction, Group 5: (E + VPA (200 mg/Kg)+FRS (100 mg/Kg, combination treatment). The treatment group received VPA for 14 days. We assessed seizures based on modified RacineÎs scores and conducted the electroencephalographic (EEG) recording. NLRP1 and NLRP3 mRNA levels, Apoptosis-associated Speck-like protein containing a caspase recruitment domain (ASC), absence in melanoma2 (AIM2) protein expression levels, and apoptosis rate of the brain cells were analyzed utilizing real-time PCR, immunohistochemistry, and tunnel assay, respectively. RESULTS: The results revealed that FRS and VPA treatment, alone or in combination, improved behavioral outcome and reduced seizure intensity in epileptic rats. The combination therapy significantly decreased the apoptosis rate NLRP1 and NLRP3 gene as well as ASC and AIM2 protein expression levels. CONCLUSION: Combination therapy protected the brain against neuronal damages in rats, and decreased the severity of epilepsy in K.A. induced rats. Reducing inflammation and apoptosis and improving the performance of behavioral testing in the K.A. induced epilepsy model increased the likelihood of success of combination therapy compared with VPA and FRS treatment alone.
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Epilepsia , Ácido Valproico , Animales , Masculino , Ratas , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Proteínas de Unión al ADN/metabolismo , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Furosemida , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Wistar , ARN Mensajero , Ácido Valproico/farmacología , Ácido Valproico/uso terapéuticoRESUMEN
Abstract Background Pain is an uncomfortable sensation in the body. Kaempferol is a flavonoid with antinociceptive effects. Transient receptor potential (TRP) channels have been characterized in the sensory system. Objective This study evaluated the central antinociceptive effect of Kaempferol and possible mechanisms of action of transient receptor potential cation channel subfamily V member 1 (TRPV1). Methods Capsaicin as a TRPV agonist (5 μg/μL, intracerebroventricular [ICV]) and capsazepine as its antagonist (10 μg/μL, icv) were used to test the analgesic effect of kaempferol (1.5 mg, ICV). Morphine (10 μg, ICV) was used as a positive control. The other groups were treated with a combination of kaempferol and capsaicin, kaempferol and capsazepine, and capsaicin and capsazepine. The cannula was implanted in the cerebroventricular area. The tail-flick, acetic acid, and formalin tests were used to assess analgesic activity.For evaluation of antiinflammatory effect, the formalin-induced rat pawedema was used. Results Kaempferol significantly decreased pain in the acute pain models, including the tail-flick and the first phase of the formalin test. In the late phase of the formalin test, as a valid model of nociception, capsazepine inhibited the antinociceptive effect of kaempferol. Conclusions Kaempferol has an analgesic effect in the acute pain model and can affect inflammatory pain. Also, the TRPV1 channel plays a role in the antinociceptive activity of kaempferol.
Resumo Antecedentes A dor é uma sensação desconfortável no corpo. Kaempferol é um flavonoide com efeitos antinociceptivos. Canais receptores de potencial transitório têm sido caracterizados no sistema sensorial. Objetivo Este estudo avaliou o efeito antinociceptivo central do kaempferol e os possíveis mecanismos de ação do TRPV1. Métodos Capsaicina como agonista de TRPV (5 μg/μL, intracerebroventricular [ICV]) e capsazepina como seu antagonista (10 μg/μL, icv) foram usados para testar o efeito analgésico do kaempferol (1,5 mg, ICV). A morfina (10 μg, ICV) foi usada como controle positivo. Os outros grupos foram tratados com uma combinação de kaempferol e capsaicina, kaempferol e capsazepina e capsaicina e capsazepina. A cânula foi implantada na área cerebroventricular. Os testes de movimento de cauda, ácido acético e formalina foram usados para avaliar a atividade analgésica. Para avaliação do efeito anti-inflamatório, foi utilizado o edema de pata de rato induzido por formalina. Resultados Kaempferol diminuiu significativamente a dor nos modelos de dor aguda, incluindo o movimento da cauda e a primeira fase do teste de formalina. Na fase tardia do teste da formalina, como modelo válido de nocicepção, a capsazepina inibiu o efeito antinociceptivo do kaempferol. Conclusões Kaempferol tem efeito analgésico no modelo de dor aguda e pode afetar a dor inflamatória. Além disso, o canal TRPV1 desempenha um papel na atividade antinociceptiva do kaempferol.
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Introduction: The leading cause of memory impairment is dementia-related disorders. Since current treatments for memory impairment target the neuroinflammatory pathways, we selected dapsone, an anti-inflammatory agent, to evaluate its effects on scopolamine-induced memory impairment in mice and the underlying role of nitric oxide (NO). Methods: Scopolamine (1 mg/kg, intraperitoneal [i.p.]) was used for induction of memory impairment. The animals received various doses of dapsone (0.1, 0.3, 1, 5, and 10 mg/kg, i.p.). Duration and number of arms visits in the Y-maze and step-through latency in the passive-avoidance were documented. To evaluate the underlying signaling pathway, N(ω)-nitro-L-arginine methyl ester (a nonspecific NO synthase [NOS] inhibitor), aminoguanidine (a specific inducible NOS inhibitor), and 7-nitroindazole (a specific neuronal NOS inhibitor) were administered 30 min after dapsone administration. Results: Dapsone (5 mg/kg) substantially improved memory acquisition in scopolamine-induced memory impairment. Additionally, NOS inhibitors considerably reversed the observed neuroprotective effects of dapsone, accompanied by the elevation of NO levels. Conclusion: Dapsone revealed a neuroprotective effect against scopolamine-induced memory impairment in mice, possibly through the nitrergic pathway.
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INTRODUCTION: Using nanoparticle (NP) drugs can have better effects on the target tissue in various diseases. Alzheimer's disease (AD) is one of the degenerative neurological diseases that due to its high prevalence, requires the use of more appropriate treatments. Therefore, the aim of this study was consideration of the effect of cannabidiol (CBD) coated by nano-chitosan on learning and memory, hippocampal cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 1 (CB2) levels, and amyloid plaques in an AD rat model. MATERIAL AND METHODS: Thirty-five male Wistar rats were randomly divided into 5 groups (n = 7 in each): control, Alzheimer's disease model that received the beta-amyloid (Aß) peptide (Alz), Alz + nano-chitosan (NP) Alz + CBD, and Alz + NP + CBD. Alz was induced by injection of the Aß1-42 peptide into the hippocampal area cornu ammonis1. After confirmation of Alz, 1 µL of CBD and NP + CBD were administered by oral gavage daily in rats for 1 month. The Morris water maze (MWM) test was used to assess learning and memory of animals. Cresyl violet staining was used for consideration of dead cells. Gene and protein expression of CB1 and CB2 was performed by real-time PCR and immunohistochemistry methods. RESULTS: Induction of Alz significantly increased Aß plaques and dead cells compared to the control group (p < 0.001). Results of MWM in the day test show that Alz + NP + CBD significantly decrease escape latency (p < 0.01), travelled distance (p < 0.001), and significantly increased spending time (p < 0.001) compared to the Alz group. Protein expression of CB1 and CB2 significantly increased in Alz + CBD and Alz + NP + CBD compared to the Alz group (p < 0.05). CONCLUSION: It seems that CBD coated by nano-chitosan has good potential for reducing Aß plaques, increasing brain CB1 and levels CB2, and improving learning and memory in Alz rats.
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Enfermedad de Alzheimer , Cannabidiol , Quitosano , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides , Animales , Cannabidiol/farmacología , Quitosano/farmacología , Hipocampo , Humanos , Masculino , Placa Amiloide , Ratas , Ratas Wistar , Receptores de CannabinoidesRESUMEN
An incapability to improve lost cardiac muscle caused by acute ischemic injury remains the most important deficiency of current treatments to prevent heart failure. We investigated whether cardiomyocytes culturing on cardiac aorta-derived extracellular matrix scaffold has advantageous effects on cardiomyocytes survival and angiogenesis biomarkers' expression. Ten male NMRI mice were randomly divided into two groups: (1) control (healthy mice) and (2) myocardial infarction (MI)-induced model group (Isoproterenol/subcutaneously injection/single dose of 85 mg/kg). Two days after isoproterenol injection, all animals were sacrificed to isolate cardiomyocytes from myocardium tissues. The fresh thoracic aorta was obtained from male NMRI mice and decellularized using 4% sodium deoxycholate and 2000 kU DNase-I treatments. Control and MI-derived cardiomyocytes were seeded on decellularized cardiac aorta (DCA) considered three-dimensional (3D) cultures. To compare, the isolated cardiomyocytes from control and MI groups were also cultured as a two-dimensional (2D) culture system for 14 days. The cell viability was examined by MTT assay. The expression levels of Hif-1α and VEGF genes and VEGFR1 protein were tested by real-time PCR and western blotting, respectively. Moreover, the amount of VEGF protein was evaluated in the conditional media of the 2D and 3D systems. The oxidative stress was assessed via MDA assay. Hif-1α and VEGF genes were downregulated in MI groups compared to controls. However, the resulting data showed that decellularized cardiac aorta matrices positively affect the expression of Hif-1α and VEGF genes. The expression level of VEGFR1 protein was significantly (p ≤ 0.01) upregulated in both MI and healthy cell groups cultured on decellularized cardiac aorta matrices as a 3D system compared to the MI cell group cultured in the 2D systems. Furthermore, MDA concentration significantly decreased in 3D-cultured cells (MI and healthy cell groups) rather than the 2D-cultured MI group (p ≤ 0.015). The findings suggest that cardiac aorta-derived extracellular scaffold by preserving VEGF, improving the cell viability, and stimulating angiogenesis via upregulating Hif-1α, VEGF, and VEGFR1 in cardiomyocytes could be considered as a potential approach along with another therapeutic method to reduce the complications of myocardial infarction and control the progressive pathological conditions related to MI.
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Aorta , Matriz Extracelular , Isoproterenol/toxicidad , Infarto del Miocardio/terapia , Neovascularización Fisiológica/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Células Musculares/efectos de los fármacos , Infarto del Miocardio/inducido químicamenteRESUMEN
BACKGROUND: Resistant Staphylococcus aureus (S. aureus) bacteria are considered among the major causes of foodborne diseases. This survey aims to assess genotypic and phenotypic profiles of antibiotic resistance in S. aureus bacteria isolated from ready-to-eat food samples. METHODS: According to the previously reported prevalence of S. aureus in ready-to-eat food samples, a total of 415 ready-to-eat food samples were collected from Tehran province, Iran. S. aureus bacteria were identified using culture and biochemical tests. Besides, the phenotypic antibiotic resistance profile was determined by disk diffusion. In addition, the genotypic pattern of antibiotic resistance was determined using the PCR. RESULTS: A total of 64 out of 415 (15.42%) ready-to-eat food samples were contaminated with S. aureus. Grilled mushrooms and salad olivieh harbored the highest contamination rate of (30%), while salami samples harbored the lowest contamination rate of 3.33%. In addition, S. aureus bacteria harbored the highest prevalence of resistance to penicillin (85.93%), tetracycline (85.93%), gentamicin (73.43%), erythromycin (53.12%), trimethoprim-sulfamethoxazole (51.56%), and ciprofloxacin (50%). However, all isolates were resistant to at least four antibiotic agents. Accordingly, the prevalence of tetK (70.31%), blaZ (64.06%), aacA-D (57.81%), gyrA (50%), and ermA (39.06%) was higher than that of other detected antibiotic resistance genes. Besides, AacA-D + blaZ (48.43%), tetK + blaZ (46.87%), aacA-D + tetK (39.06%), aacA-D + gyrA (20.31%), and ermA + blaZ (20.31%) were the most frequently identified combined genotypic patterns of antibiotic resistance. CONCLUSION: Ready-to-eat food samples may be sources of resistant S. aureus, which pose a hygienic threat in case of their consumption. However, further investigations are required to identify additional epidemiological features of S. aureus in ready-to-eat foods.
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BACKGROUND AND PURPOSE: Licofelone is a dual 5-lipoxygenase/cyclooxygenase inhibitor, with well-documented anti-inflammatory and analgesic effects, which is used for treatment of osteoarthritis. Recent preclinical studies have also suggested neuroprotective and anti-oxidative properties of this drug in some neurological conditions such as seizure and epilepsy. We have recently demonstrated a role for nitric oxide (NO) signaling in the anti-epileptic activity of licofelone in two seizure models in rodents. Given the important role of N-methyl-D-aspartate receptors (NMDARs) activation in the NO production and its function in the nervous system, in the present study, we further investigated the involvement of NMDAR in the effects of licofelone (1, 3, 5, 10, and 20 mg/kg, intraperitoneal [i.p.]) in an in vivo model of seizure in mice. METHODS: Clonic seizures were induced in male NMRI mice by intravenous administration of pentylenetetrazol (PTZ). RESULTS: Acute administration of licofelone exerted anticonvulsant effects at 10 (p<0.01) and 20 mg/kg (p<0.001). A combined treatment with sub-effective doses of the selective NMDAR antagonist MK-801 (0.05 mg/kg, i.p.) and licofelone (5 mg/kg, i.p.) significantly (p<0.001) exerted an anticonvulsant effect on the PTZ-induced clonic seizures in mice. Notably, pre-treatment with the NMDAR co-agonist D-serine (30 mg/kg, i.p.) partially hindered the anticonvulsant effects of licofelone (20 mg/kg). CONCLUSIONS: Our data suggest a possible role for the NMDAR in the anticonvulsant effects of licofelone on the clonic seizures induced by PTZ in mice.
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Studies on the bronchial vascular bed have revealed that the number of blood vessels in the lamina propria and under the mucosa of the lung tissue increases in patients suffering from mild to severe asthma. Thus, in this study, a new strategy was employed in respiratory system disorders by angiogenesis inhibition in an ovalbumin (OVA)-induced rat model of asthma. Twenty-one male Wistar albino rats, 8 weeks old, were randomly divided into three groups (n = 7 in each group), including (1) control group, (2) OVA-treated group, and (3) OVA + Bmab (bevacizumab drug). On days 1 and 8, 1 mg of OVA and aluminum hydroxide in sterile phosphate-buffered saline (PBS) were intraperitoneally injected to rats in groups 2 and 3. The control group was only subject to intraperitoneal injection of saline on days 1 and 8. One week after the last injection, the rats (groups 2 and 3) were exposed to OVA inhalation for 30 min at 2-day intervals from days 15 to 25. After sensitization and challenge with OVA, the OVA + Bmab group (group 3) were treated with a 5 mg/kg bevacizumab drug. Genes and protein expression of IL-1ß and TNF-α and the expression of vascular endothelial growth factor (VEGF) protein were assessed by real-time PCR and immunohistochemistry respectively, in lung tissue. OVA exposure increased mucosal secretion and inflammatory cell populations in lung tissue and OVA-specific IgE level in serum. Also, VEGF and cytokine factor expression were significantly elevated in the OVA-induced asthma model (p ≤ 0.05). However, rats in OVA + Bmab group showed significantly a decrease in VEGF and IL-1ß and TNF-α genes as well as proteins (p ≤ 0.05). The results showed that bevacizumab efficiently diminished bronchial inflammation via downregulation of VEGF expression, followed by inflammatory cells population and cytokines reduction. Angiogenesis inhibition in rats with induced asthma not only suppresses the inflammatory process through blocking VEGF expression but also inhibits the development of new blood vessels and progressing asthmatic attacks.
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Inhibidores de la Angiogénesis/farmacología , Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Bevacizumab/farmacología , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Neovascularización Patológica , Neumonía/tratamiento farmacológico , Animales , Asma/inducido químicamente , Asma/metabolismo , Asma/patología , Modelos Animales de Enfermedad , Células Caliciformes/efectos de los fármacos , Células Caliciformes/metabolismo , Células Caliciformes/patología , Mediadores de Inflamación/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Pulmón/metabolismo , Pulmón/patología , Masculino , Ovalbúmina , Neumonía/inducido químicamente , Neumonía/metabolismo , Neumonía/patología , Ratas Wistar , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Bevacizumab with anti-angiogenesis properties reduces the vascular endothelial growth factor (VEGF) level and has widely been used to treat various diseases such as lung diseases and chronic obstructive pulmonary disease (COPD). This study, therefore, aimed to consider the effects of bevacizumab on VEGF receptor 2 (VEGFR2) and lung inflammation of the ovalbumin-induced rat model of airway hypersensitivity. MATERIALS AND METHODS: Twenty-one male Wistar rats were randomly divided into 3 groups (n = 7 in each group): (1) control, (2) ovalbumin (OVA)-sensitized, and (3) OVA-sensitized with bevacizumab (OVA + Bmab). Groups 2 and 3 were sensitized with ovalbumin (OVA) and aluminum hydroxide on days 1, 8 and challenged with OVA on day 15 by atomization for 10 days (inhalation). After OVA sensitization, the OVA + Bmab was treated with bevacizumab for 2 weeks. VEGFR2 was semiquantitatively analyzed in the lungs by immunohistochemistry. VEGF was measured in the lung tissue by ELISA method. The mRNA of IL-10 and IL-6 lung tissue were measured by real-time PCR. RESULTS: Ovalbumin exposure promoted the expression of VEGF and resulted in inflammatory factors overexpression (p ≤ 0.05). However, rats in OVA + Bmab group showed significantly a decrease in VEGFR2 and IL-1ß, IL-6, TNFα, and an increase in IL-10 (p ≤ 0.05). CONCLUSION: The results show that bevacizumab efficiently diminishes bronchial inflammation via reducing the expression of VEGFR2, and IL-6 genes and enhancing the expression of IL-10 gene. Hence, bevacizumab could be considered as a potential candidate drug to control pathological conditions relevant to airway hypersensitivity.
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Bevacizumab/uso terapéutico , Citocinas/antagonistas & inhibidores , Ovalbúmina/toxicidad , Hipersensibilidad Respiratoria/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Bevacizumab/farmacología , Citocinas/metabolismo , Masculino , Ratas , Ratas Wistar , Hipersensibilidad Respiratoria/inducido químicamente , Hipersensibilidad Respiratoria/metabolismo , Transducción de Señal/fisiología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The present study investigates the neuroprotective effects of modafinil-coated nanoparticle in rats' hippocampal CA1 region. Male Wistar rats (n = 48) were randomly divided into four groups. Then middle cerebral artery occlusion (MCAO) was performed by inserting a silicone coat filament in the right internal carotid artery via the external carotid artery until it reached the anterior cerebral artery. Modafinil (100 mg/kg) or modafinil-coated nanoparticle (100 mg/kg) was given to the rats as an oral gavage once a day. Infarct volume, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neuronal nuclear protein (NeuN) and Caspase-3 and, Caspase-8 as apoptotic genes were measured in the hippocampal CA1 region. Cresyl violet staining revealed that modafinil nanoparticle significantly decreased the neurodegeneration. Reverse transcription polymerase chain reaction results showed that modafinil nanoparticle use significantly increased the expression of neurotrophic factors (even more than modafinil alone group; p = .01). Moreover, the apoptotic markers were significantly decreased in nanoparticle modafinil (MN group); p < .05). The western blot analysis and Immunohistochemistry results confirmed the neuroprotective and anti-apoptotic effects of modafinil nanoparticle. This study's results showed that the use of modafinil-coated nanoparticle has neuroprotective effects by increasing neurotrophic factors and reducing apoptosis after MCAO in the CA1 area of the hippocampus. However, further studies are needed especially, in human samples.
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Nanopartículas , Fármacos Neuroprotectores , Animales , Apoptosis , Factor Neurotrófico Derivado del Encéfalo , Factor Neurotrófico Derivado de la Línea Celular Glial , Hipocampo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Modafinilo , Neuronas , Fármacos Neuroprotectores/farmacología , Proteínas Nucleares , Ratas , Ratas WistarRESUMEN
In this work, agonist and antagonist N-methyl-D-aspartate (NMDA) receptor activation effect on cell fate during germ cell differentiation and regulate apoptotic process in 3D organ culture were studied. Afterwards, the effect of D-serine, retinoic acid (RA) and MK801 on spermatogenesis development was investigated. The animals were injected a single dose (40 mg/kg, intraperitoneal) of busulfan. After confirming the model, ten 5-day-old NMRI mice were used as spermatogonial stem cells (SSCs) transplantation donors. The SSCs were confirmed by detecting the promyelocytic leukaemia zinc finger (PLZF) protein. Then, tissue culture of the azoospermia model which had received SSCs was performed in various conditions (seven groups). The apoptosis markers levels of cells were significantly decreased in differentiation media containing RA and serine. In contrast, the expression of apoptotic markers including caspase 3, caspase 9 and Bax was increased in the presence of MK801. In conclusion, a new in vitro system capable of producing mature spermatozoa was developed that would be useful for investigating the medicinal effects of agents on the male reproductive system. Also, a comparison of spermatogenesis development in different media revealed that the presence of D-serine and RA (retinoic acid) in the culture medium has a positive effect on spermatogenesis.
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Receptores de N-Metil-D-Aspartato , Espermatogonias , Animales , Apoptosis , Diferenciación Celular , Masculino , Ratones , Técnicas de Cultivo de Órganos , Espermatogénesis , TestículoRESUMEN
Systemic treatments for ischemic stroke as a disease with high disability and death have been yet unsuccessful. Combined treatments can potentially cause better results in treatment of patients with Stroke. In this study we assessed the neuroprotective effect of modafinil-coated gold nanoparticles (AuNPs) and mesenchymal stem cell (MSC) in ischemic stroke rats. Stem cells and AuNPs offer great promise for new medical treatments. 60 male Wistar rats were randomly divided into five groups (12 in each group): (1) the group that developed middle cerebral artery occlusion (MCAO or ischemia), (2) the normal group (control), (3) the MCAO group that received MSC (C + MCAO), (4) the MCAO group that received MSC and modafinil (CM + MCAO), and (5) the MCAO group that received MSC and modafinil-coated AuNPs (CMN + MCAO). Middle Cerebral Artery Occlusion (MCAO) was performed by inserting a silicone coat filament in the right internal carotid artery via the external carotid artery until it reached the anterior cerebral artery. The filament was located in the internal carotid artery for 60 min and then removed. Modafinil-coated AuNPs (100 mg/kg) or Modafinil (100 mg/kg) were given to the rats as an oral gavage, once a day in the morning time. Finally, infarct volume, BDNF (Brain-derived neurotrophic factor), GDNF (Glial cell-derived neurotrophic factor), NeuN (neuronal nuclear protein) expression, and cell apoptosis in brain were analyzed. The brain infarct volume and apoptosis significantly decreased and BDNF, NeuN, and GDNF increased in C + MCAO, CM + MCAO, and CMN + MCAO groups compared to ischemia. CMN + MCAO groups did not show significant difference in these factors compared to control group. These results demonstrated that the administration of stem cells and Modafinil-coated AuNPs at the same time had a good effect on ischemic brain injuries. It happened through increasing neurotrophic factors and decreasing brain cell apoptosis.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Nanopartículas del Metal , Animales , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Modelos Animales de Enfermedad , Oro , Humanos , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Modafinilo , Ratas , Ratas WistarRESUMEN
Background: Cockroaches are one of the most important and frequent insects responsible for harboring, transmission and dissemination of human pathogens in the hospital environment. The present research was done to study the phenotypic and genotypic characterization of antibiotic resistance in the Methicillin-resistant Staphylococcus aureus strains isolated from hospital cockroaches. Methods: Five-hundred and thirty Periplanets americana and Blattella germanica cockroaches were collected and their gut content and external washing samples were subjected to bacterial isolation. MRSA strains were subjected to disk diffusion and PCR amplification of antibiotic resistance genes. Results: Prevalence of MRSA strains in P. americana and B. germanica cockroaches were 52.77 and 43.33%, respectively. External washing samples of P. americana cockroaches had the highest prevalence of MRSA strains (59.57%). MRSA isolates of external washing samples harbored the highest prevalence of resistance against penicillin (100%), ceftaroline (100%), tetracycline (100%), gentamicin (83.33%) and trimethoprim-sulfamethoxazole (80.55%). MRSA strains isolated from gut content samples harbored the highest prevalence of resistance against penicillin (100%), ceftaroline (100%), tetracycline (100%), trimethoprim-sulfamethoxazole (80%) and gentamicin (73.33%). BlaZ, aacA-D, tetK, msrA, dfrA, ermA, gyrA, grlA and rpoB were the most commonly detected antibiotic resistance genes amongst the MRSA strains. Conclusions: The present investigation is the first report of the phenotypic and genotypic evaluation of antibiotic resistance in the MRSA strains isolated from P. americana and B. germanica hospital cockroaches. Hospital cockroaches are considered as a potential mechanical vector for MRSA strains.
Asunto(s)
Proteínas Bacterianas/genética , Cucarachas/microbiología , Farmacorresistencia Bacteriana Múltiple , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Animales , Antibacterianos/farmacología , Pruebas Antimicrobianas de Difusión por Disco , Genotipo , Hospitales , Humanos , Irán/epidemiología , Staphylococcus aureus Resistente a Meticilina/genética , Fenotipo , Prevalencia , Centros de Atención TerciariaRESUMEN
Abstract Angiogenesis plays a key role in tumor growth, invasion and metastasis of cancer diseases and therefore, the inhibition of angiogenesis can provide an important therapeutic approach in cancer diseases. This study was designed to compare the anti-angiogenic activities of the ethanolic extract of Artemisia sieberi Besser, Asteraceae, and its active substance, artemisinin in both in vitro and in vivo models. To compare cytotoxicity level of ethanolic extract of A. sieberi with artemisinin, different concentrations (1–100 µg/ml) were tested using MTT assay on human umbilical vein endothelial cells. The anti-angiogenic properties of serial concentrations of ethanolic extract of A. sieberi and artemisinin were examined on human umbilical vein endothelial cells using a three-dimensional angiogenesis assay (in vitro model) and in the chick chorioallantoic membrane assay as in vivo model. The effects of ethanolic extract of A. sieberi and artemisinin were also tested on the expression of VEGFR-1, VEGFR-2 and CD34 genes using real-time PCR. Ethanolic extract of A. sieberi and artemisinin significantly (p < 0.001) inhibited the angiogenesis in the human umbilical vein endothelial cells culture whilst the ethanolic extract of A. sieberi showed higher effect in a concentration-dependent fashion (p < 0.001). The chick chorioallantoic membrane angiogenesis was also completely inhibited by ethanolic extract of A. sieberi at concentration of 33 ng/100 µl/egg. The gene expression analysis showed that the ethanolic extract of A. sieberi and artemisinin reduced the transcription of VEGFR-1, VEGFR-2 and CD34 genes in a concentration-dependent manner. This study demonstrated that the ethanolic extract of A. sieberi is strongly able to inhibit the angiogenesis in human umbilical vein endothelial cells and chick chorioallantoic membrane models compared to the artemisinin.