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Article ; Online: Functional Roles of Mesenchymal Stem Cell-derived Exosomes in Ischemic Stroke Treatment.

Farzaneh, Maryam / Khoshnam, Seyed Esmaeil

2023 Volume 19, Issue 1, Page(s) 2–14

Abstract: Stroke is a life-threatening disease and one of the leading causes of death and physical disability worldwide. Currently, no drugs on the market promote neural recovery after stroke insult, and spontaneous remodeling processes are limited to induce ... ...

Abstract	Stroke is a life-threatening disease and one of the leading causes of death and physical disability worldwide. Currently, no drugs on the market promote neural recovery after stroke insult, and spontaneous remodeling processes are limited to induce recovery in the ischemic regions. Therefore, promoting a cell-based therapy has been needed to elevate the endogenous recovery process. Mesenchymal stem cells (MSCs) have been regarded as candidate cell sources for therapeutic purposes of ischemic stroke, and their therapeutic effects are mediated by exosomes. The microRNA cargo in these extracellular vesicles is mostly responsible for the positive effects. When it comes to the therapeutic viewpoint, MSCsderived exosomes could be a promising therapeutic strategy against ischemic stroke. The aim of this review is to discuss the current knowledge around the potential of MSCs-derived exosomes in the treatment of ischemic stroke.
Language	English
Publishing date	2023-02-08
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2251937-3
ISSN	2212-3946 ; 1574-888X
ISSN (online)	2212-3946
ISSN	1574-888X
DOI	10.2174/1574888X18666221222123818
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Zs.A 6399: Show issues

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Article ; Online: Sesamin mitigates lead-induced behavioral deficits in male rats: The role of oxidative stress.

Ghaderi, Shahab / Rashno, Masome / Sarkaki, Alireza / Khoshnam, Seyed Esmaeil

Brain research bulletin

2023 Volume 206, Page(s) 110852

Abstract: Lead (Pb) is a well-known toxic pollutant that has negative effects on behavioral functions. Sesamin, a phytonutrient of the lignan class, has shown neuroprotective effects in various neurological disorder models. The present study was undertaken to ... ...

Abstract	Lead (Pb) is a well-known toxic pollutant that has negative effects on behavioral functions. Sesamin, a phytonutrient of the lignan class, has shown neuroprotective effects in various neurological disorder models. The present study was undertaken to evaluate the putative protective effects of sesamin against Pb-induced behavioral deficits and to identify the role of oxidative stress in male rats. The rats were exposed to 500 ppm of Pb acetate in their drinking water and simultaneously treated orally with sesamin at a dose of 30 mg/kg/day for eight consecutive weeks. Standard behavioral paradigms were used to assess the behavioral functions of the animals during the eighth week of the study. Subsequently, oxidative stress factors were evaluated in both the cerebral cortex and hippocampal regions of the rats. The results of this study showed that Pb exposure triggered anxiety-/depression-like behaviors and impaired object recognition memory, but locomotor activity was indistinguishable from the normal control rats. These behavioral deficiencies were associated with suppressed enzymatic and non-enzymatic antioxidant levels, and enhanced lipid peroxidation in the investigated brain regions. Notably, correlations were detected between behavioral deficits and oxidative stress generation in the Pb-exposed rats. Interestingly, sesamin treatment mitigated anxio-depressive-like behaviors, ameliorated object recognition memory impairment, and modulated oxidative-antioxidative status in the rats exposed to Pb. The results suggest that the anti-oxidative properties of sesamin may be one of the underlying mechanisms behind its beneficial effect in ameliorating behavioral deficits associated with Pb exposure.
MeSH term(s)	Rats ; Animals ; Male ; Rats, Wistar ; Lead/pharmacology ; Oxidative Stress ; Antioxidants/pharmacology ; Lignans/pharmacology ; Lignans/therapeutic use ; Dioxoles
Chemical Substances	sesamin (S7946O4P76) ; Lead (2P299V784P) ; Antioxidants ; Lignans ; Dioxoles
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2023.110852
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Article ; Online: Corrigendum to "Memory deficits and hippocampal inflammation in cerebral hypoperfusion and reperfusion in male rats: Neuroprotective role of vanillic acid" [Life Sci. 211 (2018) 126-132].

Khoshnam, Seyed Esmaeil / Sarkaki, Alireza / Rashno, Masome / Farbood, Yaghoob

Life sciences

2023 Volume 319, Page(s) 121521

Language	English
Publishing date	2023-03-04
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121521
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Article: Sesamin alleviates defects in seizure, behavioral symptoms, and hippocampus electroencephalogram in a pentylenetetrazol rat model.

Malekinia, Farima / Farbood, Yaghoob / Sarkaki, Alireza / Khoshnam, Seyed Esmaeil / Navabi, Seyedeh Parisa

Iranian journal of basic medical sciences

2023 Volume 26, Issue 9, Page(s) 1016–1023

Abstract: Objectives: Seizure is a prevalent disorder reflected by powerful and sudden activity of neural networks in the brain that leads to tonic-clonic attacks. These signs may be due to an increase in excitatory/inhibitory neurotransmitters ratio. So, the ... ...

Abstract	Objectives: Seizure is a prevalent disorder reflected by powerful and sudden activity of neural networks in the brain that leads to tonic-clonic attacks. These signs may be due to an increase in excitatory/inhibitory neurotransmitters ratio. So, the current experiment aimed to examine the seizure and neurobehavioral parameters, as well as the hippocampus local electroencephalogram (EEG) after seizure with and without sesamin pretreatment. Materials and methods: Sesamin (15, 30, and 60 mg/kg/5 ml, intraperitoneal or IP, vehicle: dimethyl sulfoxide or DMSO, for 3 days) was administrated before pentylenetetrazol (PTZ) (60 mg/kg/10 ml, IP, vehicle: saline), which induces acute seizure in adult male Wistar rats (230 ± 20 g, six weeks old). Different phases of seizures (score, latency, duration, and frequency), behavioral parameters (passive avoidance memory, anxiety, and locomotor activity), and hippocampus local EEG were evaluated after the injections. At the end of the experiments, oxidative stress markers plus gene expression of phosphoinositide 3-kinase/protein kinase B or Results: Pretreatment with sesamin (30 mg/kg) could significantly decrease seizure scores and oxidative stress in the hippocampus. PTZ injection induced EEG deficits and neurobehavioral impairments which were significantly decreased by sesamin, especially in Beta, Theta, and delta EEG waves. Also, the expression of Conclusion: Sesamin could prevent seizure attacks and neurobehavioral and EEG deficits induced by pentylenetetrazol, probably through the
Language	English
Publishing date	2023-08-16
Publishing country	Iran
Document type	Journal Article
ZDB-ID	2500485-2
ISSN	2008-3874 ; 2008-3866
ISSN (online)	2008-3874
ISSN	2008-3866
DOI	10.22038/IJBMS.2023.69565.15151
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Article ; Online: Anethole attenuates motor dysfunctions, striatal neuronal activity deficiency and blood brain barrier permeability by decreasing striatal α-synuclein and oxidative stress in rotenone-induced Parkinson's disease of male rats.

Moradi Vastegani, Sadegh / Khoshnam, Seyed Esmaeil / Ghafouri, Samireh / Bakhtiari, Nima / Farbood, Yaghoob / Sarkaki, Alireza

PloS one

2023 Volume 18, Issue 11, Page(s) e0294612

Abstract: Introduction: Anethole is the main compound of the essential oil of anise and several other plants, which has antioxidant, anti-inflammatory, and neuroprotective properties. Oxidative stress is considered as an important factor in the pathogenesis of PD. ...

Abstract	Introduction: Anethole is the main compound of the essential oil of anise and several other plants, which has antioxidant, anti-inflammatory, and neuroprotective properties. Oxidative stress is considered as an important factor in the pathogenesis of PD. In the present study, we aimed to investigate the effects of anethole against rotenone-induced PD. Methods: Male Wistar rats were randomly divided into six groups. Control group received DMSO + sunflower oil, model group received rotenone (2 mg/kg, s.c, daily for 35 days), positive control group received L-Dopa, and test groups received anethole (62.5, 125, and 250 mg/kg, i.g, daily for 35 days) 1 hour before each rotenone injection. Body weight changes, rotarod test, stride length test, and extracellular single unit recording were performed after treatment. After behavioral test, Brain water content and blood brain barrier (BBB) permeability were evaluated, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), alpha-synuclein and MAO-B were measured in the striatum. Results: Chronic administration of rotenone induced body weight loss and caused significant dysfunction in locomotor activity, neuronl firing rate, and BBB. Rotenone also decreased SOD activity, increased MDA level, and elevated the expression of alpha-synuclein and MAO-B in the striatum. However, treatment with anethole attenuated body weight loss, motor function, neuronal activity, and BBB function. Furthermore, Anethole treatment attenuated oxidative stress and decreased the expression of alpha-synuclein and MAO-B compared to the rotenone group. Conclusion: Our results show that through its antioxidant properties, aethole can improve the cellular, molecular and behavioral characteristics of rotenone-induced Parkinson's disease.
MeSH term(s)	Rats ; Animals ; Parkinson Disease/drug therapy ; Parkinson Disease/etiology ; Parkinson Disease/metabolism ; Rotenone/pharmacology ; alpha-Synuclein/metabolism ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Blood-Brain Barrier/metabolism ; Rats, Wistar ; Oxidative Stress ; Neuroprotective Agents/pharmacology ; Superoxide Dismutase/metabolism ; Monoamine Oxidase/metabolism ; Weight Loss ; Disease Models, Animal
Chemical Substances	Rotenone (03L9OT429T) ; alpha-Synuclein ; Antioxidants ; anethole (Q3JEK5DO4K) ; Neuroprotective Agents ; Superoxide Dismutase (EC 1.15.1.1) ; Monoamine Oxidase (EC 1.4.3.4)
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0294612
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Article ; Online: LncRNA MALAT1 and Ischemic Stroke: Pathogenesis and Opportunities.

Khoshnam, Seyed Esmaeil / Moalemnia, Arash / Anbiyaee, Omid / Farzaneh, Maryam / Ghaderi, Shahab

Molecular neurobiology

2023

Abstract: Ischemic stroke (IS) stands as a prominent cause of mortality and long-term disability around the world. It arises primarily from a disruption in cerebral blood flow, inflicting severe neural injuries. Hence, there is a pressing need to comprehensively ... ...

Abstract	Ischemic stroke (IS) stands as a prominent cause of mortality and long-term disability around the world. It arises primarily from a disruption in cerebral blood flow, inflicting severe neural injuries. Hence, there is a pressing need to comprehensively understand the intricate mechanisms underlying IS and identify novel therapeutic targets. Recently, long noncoding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules with the potential to attenuate pathogenic mechanisms following IS. Among these lncRNAs, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) has been extensively studied due to its involvement in the pathophysiological processes of IS. In this review, we provide an in-depth analysis of the essential role of MALAT1 in the development and progression of both pathogenic and protective mechanisms following IS. These mechanisms include oxidative stress, neuroinflammation, cell death signaling, blood brain barrier dysfunction, and angiogenesis. Furthermore, we summarize the impact of MALAT1 on the susceptibility and severity of IS. This review highlights the potential risks associated with the therapeutic use of MALAT1 for IS, which are attributable to the stimulatory action of MALAT1 on ischemia/reperfusion injury. Ultimately, this review sheds light on the potential molecular mechanisms and associated signaling pathways underlying MALAT1 expression post-IS, with the aim of uncovering potential therapeutic targets.
Language	English
Publishing date	2023-12-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03853-3
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Zs.A 2411: Show issues

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Article ; Online: Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Belali, Rafie / Mard, Seyyed Ali / Khoshnam, Seyed Esmaeil / Bavarsad, Kowsar / Sarkaki, Alireza / Farbood, Yaghoob

Neuropeptides

2023 Volume 101, Page(s) 102336

Abstract: Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in ... ...

Abstract	Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.
MeSH term(s)	Rats ; Male ; Animals ; Orexins/metabolism ; Hypothalamic Area, Lateral/metabolism ; Sleep Deprivation/metabolism ; Endocannabinoids/metabolism ; Receptor, Cannabinoid, CB1/metabolism ; Rats, Wistar ; Interleukin-4/metabolism ; Interleukin-4/pharmacology ; Interleukin-6/metabolism ; Interleukin-6/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Hypothalamus/metabolism ; Neurons/metabolism ; Eating/physiology ; RNA, Messenger/metabolism ; Orexin Receptors/metabolism
Chemical Substances	Orexins ; anandamide (UR5G69TJKH) ; Endocannabinoids ; Receptor, Cannabinoid, CB1 ; Interleukin-4 (207137-56-2) ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; RNA, Messenger ; Orexin Receptors
Language	English
Publishing date	2023-04-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	9048-7
ISSN	1532-2785 ; 0143-4179
ISSN (online)	1532-2785
ISSN	0143-4179
DOI	10.1016/j.npep.2023.102336
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Article ; Online: Anandamide Attenuates Neurobehavioral Deficits and EEG Irregularities in the Chronic Sleep Deprivation Rats: The Role of Oxidative Stress and Neuroinflammation.

Belali, Rafie / Mard, Seyyed Ali / Khoshnam, Seyed Esmaeil / Bavarsad, Kowsar / Sarkaki, Alireza / Farbood, Yaghoob

Neurochemical research

2023 Volume 49, Issue 6, Page(s) 1541–1555

Abstract: Sleep deprivation increases stress, anxiety, and depression by altering the endocannabinoid system's function. In the present study, we aimed to investigate the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) in the ... ...

Abstract	Sleep deprivation increases stress, anxiety, and depression by altering the endocannabinoid system's function. In the present study, we aimed to investigate the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) in the chronic sleep deprivation (SD) model in rats. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation + 20 mg/kg AEA (SD + A). The rats were kept in a sleep deprivation device for 18 h (7 to 1 a.m.) daily for 21 days. Open-field (OFT), elevated plus maze, and forced swimming tests (FST) were used to assess anxiety and depression-like behavior. As well as the cortical EEG, CB1R mRNA expression, TNF-α, IL-6, IL-4 levels, and antioxidant activity in the brain were examined following SD induction. AEA administration significantly increased the time spent (p < 0.01), the distance traveled in the central zone (p < 0.001), and the number of climbing (p < 0.05) in the OFT; it also increased the duration and number of entries into the open arms (p < 0.01 and p < 0.05 respectively), and did not reduce immobility time in the FST (p > 0.05), AEA increased CB1R mRNA expression in the anterior and medial parts of the brain (p < 0.01), and IL-4 levels (p < 0.05). AEA also reduced IL-6 and TNF-α (p < 0.05) and modulated cortical EEG. AEA induced anxiolytic-like effects but not anti-depressant effects in the SD model in rats by modulating CB1R mRNA expression, cortical EEG, and inflammatory response.
MeSH term(s)	Animals ; Endocannabinoids/metabolism ; Sleep Deprivation/complications ; Sleep Deprivation/metabolism ; Sleep Deprivation/drug therapy ; Male ; Arachidonic Acids/pharmacology ; Rats, Wistar ; Polyunsaturated Alkamides/pharmacology ; Oxidative Stress/drug effects ; Electroencephalography ; Rats ; Anxiety/drug therapy ; Neuroinflammatory Diseases/drug therapy ; Neuroinflammatory Diseases/metabolism ; Depression/drug therapy ; Depression/metabolism ; Receptor, Cannabinoid, CB1/metabolism ; Behavior, Animal/drug effects ; Anti-Anxiety Agents/pharmacology ; Anti-Anxiety Agents/therapeutic use
Chemical Substances	anandamide
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	199335-5
ISSN	1573-6903 ; 0364-3190
ISSN (online)	1573-6903
ISSN	0364-3190
DOI	10.1007/s11064-023-04054-z
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Article ; Online: Sesamin: Insights into its protective effects against lead-induced learning and memory deficits in rats.

Rashno, Masome / Sarkaki, Alireza / Ghaderi, Shahab / Khoshnam, Seyed Esmaeil

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)

2022 Volume 72, Page(s) 126993

Abstract: Background: Lead (Pb) is one of the most hazardous pollutants that induce a wide spectrum of neurological changes such as learning and memory deficits. Sesamin, a phytonutrient of the lignan class, exhibits anti-inflammatory, anti-apoptotic, and ... ...

Abstract	Background: Lead (Pb) is one of the most hazardous pollutants that induce a wide spectrum of neurological changes such as learning and memory deficits. Sesamin, a phytonutrient of the lignan class, exhibits anti-inflammatory, anti-apoptotic, and neuroprotective properties. The present study was designed to investigate the effects of sesamin against Pb-induced learning and memory deficits, disruption of hippocampal theta and gamma rhythms, inflammatory response, inhibition of blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, Pb accumulation, and neuronal loss in rats. Methods: Sesamin treatment (30 mg/kg/day; P.O.) was started simultaneously with Pb acetate exposure (500 ppm in standard drinking water) in rats, and they continued for eight consecutive weeks. Results: The results showed that chronic exposure to Pb disrupted the learning and memory functions in both passive-avoidance and water-maze tests, which was accompanied by increase in spectral theta power and theta/gamma ratio, and a decrease in spectral gamma power in the hippocampus. Additionally, Pb exposure resulted in an enhanced tumor necrosis factor-alpha (TNF-α) content, decreased interleukin-10 (IL-10) production, inhibited blood δ-ALA-D activity, increased Pb accumulation, and neuronal loss of rats. In contrast, sesamin treatment improved all the above-mentioned Pb-induced pathological changes. Conclusion: This data suggests that sesamin could improve Pb-induced learning and memory deficits, possibly through amelioration of hippocampal theta and gamma rhythms, modulation of inflammatory status, restoration of the blood δ-ALA-D activity, reduction of Pb accumulation in the blood and the brain tissues, and prevention of neuronal loss.
MeSH term(s)	Animals ; Dioxoles ; Gamma Rhythm ; Hippocampus ; Lead/toxicity ; Lignans/pharmacology ; Lignans/therapeutic use ; Maze Learning ; Memory Disorders/chemically induced ; Memory Disorders/drug therapy ; Memory Disorders/pathology ; Rats
Chemical Substances	Dioxoles ; Lignans ; Lead (2P299V784P) ; sesamin (S7946O4P76)
Language	English
Publishing date	2022-05-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1236267-0
ISSN	1878-3252 ; 1611-602X ; 0946-672X
ISSN (online)	1878-3252 ; 1611-602X
ISSN	0946-672X
DOI	10.1016/j.jtemb.2022.126993
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Article: Yes-Associated Protein and PDZ Binding Motif: A Critical Signaling Pathway in the Control of Human Pluripotent Stem Cells Self-Renewal and Differentiation

Shi, Jia / Farzaneh, Maryam / Khoshnam, Seyed Esmaeil

Cellular reprogramming. 2020 Apr. 01, v. 22, no. 2

2020

Abstract: Human pluripotent stem cells (hPSCs) can self-renew indefinitely to generate cells like themselves with a normal karyotype and differentiate into other types of cells when stimulated with a proper set of internal and external signals. hPSCs including ... ...

Abstract	Human pluripotent stem cells (hPSCs) can self-renew indefinitely to generate cells like themselves with a normal karyotype and differentiate into other types of cells when stimulated with a proper set of internal and external signals. hPSCs including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are an alternative approach toward stem cell biology, drug discovery, disease modeling, and regenerative medicine. hESCs are commonly derived from the inner cell mass of preimplantation embryos and can maintain their pluripotency in appropriate culture media. The Hippo pathway is a major integrator of cell surface-mediated signals and plays an essential role in regulating hESCs function. Yes-associated protein (YAP) and TAZ (PDZ binding motif) are critical downstream transcriptional coactivators in the Hippo pathway. The culture conditions have effects on the cytoplasmic or nuclear YAP/TAZ localization. Also, the activity of Hippo pathway is influenced by cell density, mechanical tension, and biochemical signals. In this review article, we summarize the function of YAP/TAZ and focus on the regulation of YAP/TAZ in self-renewal and differentiation of hESCs.
Keywords	culture media ; embryonic stem cells ; humans ; induced pluripotent stem cells ; karyotyping ; medicine ; models ; signal transduction ; transcription (genetics)
Language	English
Dates of publication	2020-0401
Size	p. 55-61.
Publishing place	Mary Ann Liebert, Inc.
Document type	Article
ZDB-ID	2542436-1
ISSN	2152-4998 ; 1557-7457 ; 2152-4971
ISSN (online)	2152-4998 ; 1557-7457
ISSN	2152-4971
DOI	10.1089/cell.2019.0084
Database	NAL-Catalogue (AGRICOLA)

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