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[This corrects the article DOI: 10.3389/fphar.2023.1305816.].
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BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD), defined as the accumulation of >5% fat in the liver, is the most frequently co-exist disease with diabetics up to 70%. Current study was conducted to compare efficacy of combination therapy of empagliflozin (EMPA) or pioglitazone (PGZ) with metformin (MET) in patients with T2DM and NAFLD. METHODS: In this open label, prospective clinical trial, sixty patients were randomly assigned to receive EMPA 10 mg/day or PGZ 30 mg/day in combination Metformin (at least 1500 mg) for six months. NAFLD grade and liver stiffness were defined and measured at the beginning and after 6 months. As the secondary outcomes, anthropometric characteristics, lipid profile, plasma glucose test, and liver enzymes test were measured at the baseline and endpoint. RESULTS: The results showed that both combination therapy with EMPA+ MET or PGZ+MET significantly reversed fibrosis stage of NAFLD (P<0.05). Significant reduction in lipid profile test, and liver enzymes test were seen in both groups (P<0.05). However, the greater reduction in waist circumference was observed in EMPA groups compared to PGZ (-4.4 ± 2.39 vs -2.05±1.28, p<0.001), meanwhile weight and BMI decreased significantly only in the patients receiving EMPA (-5.78 ± 3.6 kg vs 0.93 ± 0.33 kg and -2.01± 3.19 kg/m2 vs 0.33 ± 0.12 kg/m2, respectively, P<0.001). CONCLUSION: combination of EMPA or PGZ with metformin equally improved liver fibrosis stage and stiffness in T2DM patients with NAFLD. The improvements of laboratory tests were observed in the both groups, while, regarding weight reduction, only the regimen containing EMPA was effective.
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Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Metformina , Enfermedad del Hígado Graso no Alcohólico , Humanos , Pioglitazona/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Estudios Prospectivos , LípidosRESUMEN
Introduction and importance: The Masquelet technique remains one of the procedures with low rates of failure and infection. The use of this technique in humeral defects is still rare. Case presentation: A 38-year-old male patient with an open humeral comminuted fracture induced by shotgun injury was referred to our hospital. The Masquelet technique was chosen as the best option with a lower risk of infection and the lower expenses at this stage due to the second time of open reduction and internal fixation and bone graft failure, low patient compliance, and the increasing size of the defect due to bone absorption. An arthrodesis procedure was performed 5 days after the second Masquelet stage as restoring the elbow joint's range of motion was impossible. Clinical discussion: The Masquelet technique, is a two-step surgical procedure to manage pseudoarthroses and bone defects. Various surgical options are available for performing this procedure. There are several reasons behind the rising popularity of this technique during recent years. Some of these reasons include the reproducibility of this technique, as well as requiring less time, not being technically challenging, and having fewer neurovascular complications. Conclusion: This case was one of the limited examples of successful implementation of the Masquelete procedure on severe traumatic injuries of the upper limb with bone defects providing more evidence on the safety and efficacy of this technique in similar conditions.
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Insomnia is repeated difficulty in falling asleep, maintaining sleep, or experiencing low-quality sleep, resulting in some form of daytime disturbance. Sleeping disorders cause daytime fatigue, mental confusion, and over-sensitivity due to insufficient recovery from a sound sleep. There are some drugs, such as benzodiazepines and anti-histaminic agents, which help to sleep induction and insomnia cure. However, the prolonged administration is unsuitable because of tolerance and dependence. Therefore, the researchers attempt to find new medicines with lesser adverse effects. Natural products have always been good sources for developing new therapeutics for managing diseases such as cancer,cardiovascular disease, diabetes, insomnia, and liver and renal problems. Ample research has justified the acceptable reason and relevance of the use of these herbs in the treatment of insomnia. It is worth noting that in this study, we looked into various Persian herbs in a clinical trial and in vivo to treat insomnia, such as Artemisia annua, Salvia reuterana, Viola tricolor, Passiflora incarnata, lettuce, and Capparis spinose. According to research, herb extracts and fractions, particularly n-butanol fractions with non-polar agents, impact the benzodiazepine receptors and have hypnotic properties. Also, alkaloids, glycosides, flavonoids, saponins, and tannins in practically every plant are mentioned making them the popular natural compounds to help with sleep disorders and promote calmness.
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PURPOSE: Multiple genome-wide and candidate-gene association studies have been conducted to search for common risk variants of breast cancer. Recent large meta-analyses and consolidating evidence have highlighted the role of the caspase-8 gene in breast cancer pathogenesis. Therefore, this study aimed to identify common variations and haplotypes associated with risk and overall survival of breast cancer with respect to underlying susceptibility variants in the CASP8 gene region in a group of the Iranian population. METHODS: In a case-control study with a total of 1008 samples (455 cases and 553 controls), genotyping of 12 candidate polymorphisms, consisting of rs3834129, rs2037815, rs7608692, rs12990906, rs3769821, rs6435074, rs3754934, rs3817578, rs10931936, rs1045485, rs1045487, and rs13113, were performed using PCR-based methods, including ARMS-PCR, AS-PCR, RFLP-PCR, HRM-PCR, and TaqMan-PCR. RESULTS: rs3834129, rs3754934, rs12990906, and rs10931936 were associated with the risk and overall survival of breast cancer. Several haplotypes were also identified an associated with a higher risk of breast cancer, including a three-SNP haplotype rs3817578-rs10931936-rs1045485 [p < 0.001, OR = 1.78(1.32-2.41)]. rs3754934-C allele showed an association with a lower risk of death in all patients [p = 0.022; HR = 0.46(0.23-0.89)] and in the hormone-receptor-positive group [p = 0.038; HR = 0.37(0.14-0.95)], as well as CC genotype in the hormone-receptor-positive group [p = 0.002; HR = 0.09(0.02-0.43)]. CONCLUSION: The present study suggests a diagnostic and prognostic role of CASP8 gene variations in breast cancer. The risky haplotypes are likely to have one or more underlying breast cancer susceptibility alleles. Understanding the mode of action of these alleles will aid individual-level risk prediction. It also may help identify at-risk patients to provide them with better surveillance.
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Neoplasias de la Mama , Caspasa 8 , Femenino , Humanos , Alelos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Caspasa 8/genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Irán , Polimorfismo de Nucleótido SimpleRESUMEN
One of the deadliest types of CNS primary brain cancers is glioblastoma multiforme (GBM), and the survival rate of patients is about 7.2%. The standard treatment for GBM is surgical interventions followed by temozolomide. We investigated for the first time, the cytotoxic impacts of Psidium guajava (P. guajava) on the U87 GBM cell line. We measured cell toxicity through the MTT test following 24 h, 48 h, and 72 h treatment with different concentrations of fruit and seed hydroalcoholic extracts of P. guajava (25-400 µg/ml). Lipid peroxidation assay, reactive oxygen species (ROS) production, and apoptosis rate were evaluated 24 h after treatment by extracts of P. guajava. Moreover, to determine the Bax/Bcl-2 and NF-κB genes expression, we performed a real-time polymerase chain reaction (RT-PCR). Our finding demonstrated that 50-400 µg/ml of P. guajava extracts dose-dependently decreased the viability of U87 cells. Also, treatment by extracts increased lipid peroxidation, ROS production, and apoptosis in a dose-dependent manner. Moreover, the RT-PCR demonstrated an up-regulation in Bax\Bcl-2 and NF-κB. Thus, P. guajava inhibited the proliferation of U87 GBM cells and increased apoptosis probably through Bax/Bcl-2 and NF-κB regulation.
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Glioblastoma , Psidium , Humanos , Glioblastoma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Psidium/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Extractos Vegetales/farmacología , ApoptosisRESUMEN
BACKGROUND: Different chemical toxicants or natural toxins can damage human health through various routes such as air, water, fruits, foods, and vegetables. PURPOSE: Herbal medicines may be safe and selective for the prevention of toxic agents due to their active ingredients and various pharmacological properties. According to the beneficial properties of pomegranate, this paper summarized the protective effects of this plant against toxic substances. STUDY DESIGN: In this review, we focused on the findings of in vivo and in vitro studies of the protective effects of pomegranate (Punica granatum) and its active components including ellagic acid and punicalagin, against natural and chemical toxic agents. METHODS: We collected articles from the following databases or search engines such as Web of Sciences, Google Scholar, Pubmed and Scopus without a time limit until the end of September 2022. RESULTS: P. granatum and its constituents have shown protective effects against natural toxins such as aflatoxins, and endotoxins as well as chemical toxicants for instance arsenic, diazinon, and carbon tetrachloride. The protective effects of these compounds are related to different mechanisms such as the prevention of oxidative stress, and reduction of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2(COX-2) and nuclear factor ĸB (NF-ĸB) as well as the modulation of apoptosis, mitogen-activated protein kinase (MAPK) signaling pathways and improvement of liver or cardiac function via regulation of enzymes. CONCLUSION: In this review, different in vitro and in vivo studies have shown that P. granatum and its active constituents have protective effects against natural and chemical toxic agents via different mechanisms. There are no clinical trials on the protective effects of P. granatum against toxic agents.
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Lythraceae , Granada (Fruta) , Humanos , Frutas/química , Extractos Vegetales/uso terapéutico , Lythraceae/química , Antioxidantes/farmacologíaRESUMEN
Numerous studies have indicated the pharmacological properties of linalool, a volatile terpene alcohol found in many flowers and spice plants, including anti-nociceptive, anti-inflammatory, and neuroprotective activities. The aim of this study was to explore the mechanisms of neuroprotection provided by (±) linalool and its enantiomer, (R)-(-) linalool against oxygen, and glucose deprivation/reoxygenation (OGD/R) in PC12 cells. PC12 cells were treated with (±) linalool and (R)-(-) linalool before exposure to OGD/R condition. Cell viability, reactive oxygen species (ROS) production, malondialdehyde (MDA) level, DNA damage, and the levels of proteins related to apoptosis were evaluated using MTT, comet assay, and western blot analysis, respectively. IC50 values for the PC12 cells incubated with (±) linalool and (R)-(-) linalool were 2700 and 2600 µM after 14 h, as well as 5440 and 3040 µM after 18 h, respectively. Survival of the ischemic cells pre-incubated with (±) linalool and (R)-(-) linalool (100 µM of both) increased compared to the cells subjected to the OGD/R alone (p < .001). ROS and MDA formation were also decreased following incubation with (±) linalool and (R)-(-) linalool compared to the OGD/R group (p < .01). In the same way, pre-treatment with (±) linalool and (R)-(-) linalool significantly reduced OGD/R-induced DNA injury compared to that seen in OGD/R group (p < .001). (±) Linalool and (R)-(-) linalool also restored Bax/Bcl-2 ratio and cleaved caspase-3 and caspase-9 (p < .001, p < .01) following ischemic injury. The neuroprotective effect of linalool against ischemic insult might be mediated by alleviation of oxidative stress and apoptosis.
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Different toxins, including chemicals and natural, can be entered from various routes and influence human health. Herbal medicines and their active components can attenuate the toxicity of agents via multiple mechanisms. For example, kaempferol, as a flavonoid, can be found in fruits and vegetables, and has an essential role in improving disorders such as cardiovascular disorders, neurological diseases, cancer, pain, and inflammation situations. The beneficial effects of kaempferol may be related to the inhibition of oxidative stress, attenuation of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor ĸB (NF-ĸB) as well as the modulation of apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways. This flavonoid boasts a wide spectrum of toxin targeting effects in tissue fibrosis, inflammation, and oxidative stress thus shows promising protective effects against natural and chemical toxin induced hepatotoxicity, nephrotoxicity, cardiotoxicity, neurotoxicity, lung, and intestinal in the in vitro and in vivo setting. The most remarkable aspect of kaempferol is that it does not focus its efforts on just one organ or one molecular pathway. Although its significance as a treatment option remains questionable and requires more clinical studies, it seems to be a low-risk therapeutic option. It is crucial to emphasize that kaempferol's poor bioavailability is a significant barrier to its use as a therapeutic option. Nanotechnology can be a promising way to overcome this challenge, reviving optimism in using kaempferol as a viable treatment agent against toxin-induced disorders.
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FN-kappa B , Transducción de Señal , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Quempferoles/farmacología , Estrés Oxidativo , Inflamación/patología , Flavonoides/farmacologíaRESUMEN
BACKGROUND: Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice. METHODS: The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD50. RESULTS: The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n-butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD50 value was obtained as 4.8 g/kg. CONCLUSION: This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors.
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Datura stramonium , Trastornos del Inicio y del Mantenimiento del Sueño , Ratas , Ratones , Animales , Pentobarbital/farmacología , Factor Neurotrófico Derivado del Encéfalo , Extractos Vegetales/farmacología , Hipnóticos y Sedantes/farmacología , Sueño , Naloxona/farmacologíaRESUMEN
BACKGROUND: Glutamate-induced neuronal cell death plays a key role in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Some recent studies reported the potential immunomodulatory and neuroprotective properties of inhibitors of serine-threonine kinase, mTOR (mammalian target of rapamycin). However, no study was conducted about the neuroprotective potential of everolimus (EVR), a selective and potent mTOR inhibitor. Therefore, this study was planned to investigate whether EVR has protective effects against glutamate-induced toxicity in PC12 cells, which are used as model for neurons injury, and to elucidate the underlying mechanism. METHODS: PC12 cells were concurrently treated with glutamate (8 mM) and EVR (0-40 nM) for 24 h. Then, the cells viability, apoptosis rate, and apoptosis-related proteins (caspase-3, bax and bcl-2) were measured using MTT, annexin V/PI and immunoblotting assays. RESULTS: Analyzing the protective effect of different concentrations of EVR (0-40 nM) against glutamate-induced cytotoxicity revealed a significant increase in cell viability in co-treatment regimen (p < 0.01). Also, EVR (40 nM) significantly (p < 0.01) inhibited glutamate-induced apoptosis through depressing the elevation of bax/bcl-2 ratio and expression of cleaved caspase-3, concentration depend. CONCLUSION: The results demonstrated, for the first time, that EVR could protect against glutamate-mediated PC12 cell death via inhibiting apoptosis.
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Ácido Glutámico , Fármacos Neuroprotectores , Ratas , Animales , Ácido Glutámico/toxicidad , Caspasa 3/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/farmacología , Everolimus/farmacología , Células PC12 , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/farmacología , Apoptosis/fisiología , Proteínas Reguladoras de la Apoptosis , Supervivencia Celular , Fármacos Neuroprotectores/farmacología , Mamíferos/metabolismoRESUMEN
Introduction: Oxidative stress is a major instigator of various cardiovascular diseases, including myocardial infarction (MI). Despite available drugs, there is still an increased need to look for alternative therapies or identify new bioactive compounds. Sanguisorba minor (S. minor) is a native herb characterized by its potent antioxidant activity. This study was designed to evaluate the effect of S. minor against isoprenaline-induced MI. Methods: Rats were treated with the hydro-ethanolic extract of the aerial parts of S. minor at doses of 100 or 300 mg/kg orally for 9 days. Isoprenaline was injected subcutaneously at the dose of 85 mg/kg on days 8 and 9. Then, the activities of various cardiac injury markers including cardiac troponin (cTnT), lactate dehydrogenase (LDH), creatinine kinase muscle brain (CK-MB), creatinine phosphokinase (CPK), and antioxidant enzymes in serum were determined. Malondialdehyde (MDA) and thiol content were measured in cardiac tissue, and histopathological analysis was conducted. Results: Our results show that isoprenaline increased the serum levels of cTnT, LDH, CK-MB, and CPK (p < 0.001) and elevated MDA levels (p < 0.001) in cardiac tissue. Isoprenaline also reduced superoxide dismutase (SOD), catalase, and thiol content (p < 0.001). Importantly, the extract abolished isoprenaline-induced MI by elevating SOD and catalase (p < 0.001), reducing levels of MDA, and diminishing levels of cTnT, LDH, CK-MB, and CPK cardiac markers (p < 0.001). Histopathological studies of the cardiac tissue showed isoprenaline-induced injury that was significantly attenuated by the extract. Conclusion: Our results suggest that S. minor could abrogate isoprenaline-induced cardiac toxicity due to its ability to mitigate oxidative stress.
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Background and purpose: Ferula gummosa (F. gummosa), a potent medicinal herb, has been shown to possess anticancer activities in vitro. The present examination evaluated the cytotoxic and apoptogenic impacts of F. gummosa gum on the U87 glioblastoma cells. Experimental approach: MTT assay to determine the cell viability, flow cytometry by annexin V/FITC-PI to apoptosis evaluation, reactive oxygen species (ROS) assay, and quantitative RT-PCR were performed. Findings / Results: The results revealed that F. gummosa inhibited the growth of U87 cells in a concentration- and time-dependent manner with IC50 values of 115, 82, and 52 µg/mL obtained for 24, 48, and 72 h post-treatment, respectively. It was also identified that ROS levels significantly decreased following 4, 12, and 24 h after treatment. The outcomes of flow cytometry analysis suggested that F. gummosa induced a sub-G1 peak which translated to apoptosis in a concentration-dependent manner. Further examination revealed that F. gummosa upregulated Bax/Bcl-2 ratio and p53 genes at mRNA levels. Conclusion and implications: Collectively, these findings indicate that sub-G1 apoptosis and its related genes may participate in the cytotoxicity of F. gummosa gum in U87 cells.
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Abdominal aortic aneurysm (AAA) is a prevalent condition which causes progressive growth and rupture of aortic wall with a high death rate. Several studies have found that treatment with statins may decrease the progress of AAA and the risk of rupture by suppressing the inflammatory mediators, decreasing oxidative stress, and inhibiting mechanisms involved in extracellular matrix (ECM) degradation. Moreover, some studies have reported that prehospital therapy with statins can decrease mortality after surgery. The novelty of this paper is that different studies including those performed in humans and animals were reviewed and the potential mechanisms by which statins can have an effect on AAA were summarized. Overall, the evidence suggested an association between treatment with statins and improvement of AAA.
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Aneurisma de la Aorta Abdominal , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Animales , Aorta/metabolismo , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/metabolismo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Mediadores de Inflamación/metabolismo , Estrés OxidativoRESUMEN
Objective: The clinical use of tacrolimus is limited due to its side effects. This research investigated the protective activities of pomegranate seed oil (PSO) against TAC toxicity. Materials and Methods: The groups are included normal (1 ml of corn oil), TAC (2 mg/kg), and co-treatment of PSO (0.4 and 0.8 ml/kg) and TAC. All administrations were carried out intraperitoneally for 14 days. After the last injection, blood was collected from the heart. Results: TAC increased creatinine and urea. Increased malondialdehyde, reduced thiol content and superoxide dismutase. The elevation of lactate dehydrogenase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase-MB and creatinine phosphokinase that confirmed cardiac toxicity. PSO reduced TAC toxicity. PSO decreased TAC-induced pathology injury. Conclusion: PSO reduced TAC toxicity in renal and heart via scavenging free radicals.
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Objectives: The immune system plays a critical defence role against infections, injuries, and carcinogenic stimuli. As the macrophages of the brain resides in the innate immune system, microglia and their polarisation (M 1/M 2) play regulatory roles in inflammation in CNS, such as Parkinson's, Alzheimer's, dementia complex, and multiple sclerosis. Nigella sativa belongs to the Ranunculaceae family and has different anti-inflammatory and antioxidant effects. We conducted this study to evaluate the anti-inflammatory and protective properties of N. sativa oil (NSO) on the microglial cells and their polarisation (M 1/M 2) in the presence of LPS as a model of neuroinflammation. Methods: The protective effects of NSO (10-40 µg/ml) were studied on the LPS-induced microglial cells, and the levels of tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, prostaglandin E2 (PGE2), and IL-10 were evaluated using both ELISA and gene expression methods. The levels of cyclooxygenase-2 (COX-2), inducible NOS (iNOS), and arginase-1 (Arg1) were also evaluated using the real-time PCR method. In addition, nitrite oxide (NO) and urea were measured using biochemical methods. Results: NSO decreased LPS-induced toxicity at all doses (P < 0.001). NSO (10-40 µg/ml) also significantly reduced the levels of TNF-α, PGE2, IL-1ß, and IL-6 in the presence of LPS (P < 0.01 to 0.001). Pretreatment with NSO attenuated the levels of iNOS but increased Arg1 (P < 0.001). The ratio of iNOS/Arg1 was also decreased in the presence of NSO (P < 0.001) than that of the LPS group (P < 0.001). Conclusion: NSO attenuated LPS-induced inflammation and increased microglia's anti-inflammatory status. These results may prove that NSO is potentially an immunomodulator for various neurodegenerative diseases by M1 phenotype dominancy, such as Alzheimer's and Parkinson's diseases.
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Background: Doxorubicin as an anti-cancer drug causes cardiotoxicity, limiting its tolerability and use. The mechanism of toxicity is due to free radical production and cardiomyocytes injury. This research evaluated Rheum turkestanicum (R.turkestanicum) extract against doxorubicin cardiotoxicity due to its considerable in vitro antioxidant activity. Methods: Male Wistar rats received 2.5 mg/kg doxorubicin intraperitoneally every other day for 2 weeks to create an accumulative dose. R. turkestanicum was administrated at a dose of 100 and 300 mg/kg intraperitoneally from the second week for 7 days. On the 15th day, the animals were anesthetized and blood was collected from cardiac tissue for evaluation of alanine aminotransferase (ALT), cardiac muscle creatinine kinase (CK-MB), troponin T (cTn-T), lactate dehydrogenase (LDH), and B-type natriuretic peptide brain natriuretic peptide. A cardiac homogenate was also collected to determine superoxide dismutase (SOD), catalase Catalase Activity, malondialdehyde (MDA), and thiols. Histopathology was also performed. Results: Doxorubicin increased all cardiac enzymes and malondialdehyde, correlating with a reduction in SOD, catalase, and thiols. Histopathology revealed extracellular edema, moderate congestion, and hemorrhage of foci. In contrast, administration of R. turkestanicum ameliorated these doxorubicin-induced pathophysiological changes. Conclusion: This study revealed that the extract ameliorated doxorubicin-induced cardiac toxicity via modulation of oxidative stress-related pathways. Liquid chromatography-mass spectrometry analysis of R. turkestanicum indicated several components with potent pharmacological properties.
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Epilepsy affects about 1% of the population and approximately 30% of epileptic patients are resistant to current antiepileptic drugs. As a hallmark in epileptic tissue, many of the epileptic patients show changes in glia morphology and function. There are characteristic changes in different types of glia in different epilepsy models. Some of these changes such as astrogliosis are enough to provoke epileptic seizures. Astrogliosis is well known in mesial temporal lobe epilepsy (MTLE), the most common form of refractory epilepsy. A better understanding of astrocytes alterations could lead to novel and efficient pharmacological approaches for epilepsy. In this review, we present the alterations of astrocyte morphology and function and present some instances of targeting astrocytes in seizure and epilepsy.
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Epilepsia del Lóbulo Temporal , Epilepsia , Anticonvulsivantes/uso terapéutico , Astrocitos , Hipocampo , HumanosRESUMEN
BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.