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Article ; Online: New Insight Into Mechanisms of Hepatic Encephalopathy

Ali Sepehrinezhad / Ali Shahbazi / Sajad Sahab Negah / Fin Stolze Larsen

Bioinformatics and Biology Insights, Vol

An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets

2023 Volume 17

Abstract: Hepatic encephalopathy (HE) is a set of complex neurological complications that arise from advanced liver disease. The precise molecular and cellular mechanism of HE is not fully understood. Differentially expressed genes (DEGs) from microarray ... ...

Abstract	Hepatic encephalopathy (HE) is a set of complex neurological complications that arise from advanced liver disease. The precise molecular and cellular mechanism of HE is not fully understood. Differentially expressed genes (DEGs) from microarray technologies are powerful approaches to obtain new insight into the pathophysiology of HE. We analyzed microarray data sets of cirrhotic patients with HE from Gene Expression Omnibus to identify DEGs in postmortem cerebral tissues. Consequently, we uploaded significant DEGs into the STRING to specify protein-protein interactions. Cytoscape was used to reconstruct the genetic network and identify hub genes. Target genes were uploaded to different databases to perform comprehensive enrichment analysis and repurpose new therapeutic options for HE. A total of 457 DEGs were identified in 2 data sets totally from 12 cirrhotic patients with HE compared with 12 healthy subjects. We found that 274 genes were upregulated and 183 genes were downregulated. Network analyses on significant DEGs indicated 12 hub genes associated with HE. Enrichment analysis identified fatty acid beta-oxidation, cerebral organic acidurias, and regulation of actin cytoskeleton as main involved pathways associated with upregulated genes; serotonin receptor 2 and ELK-SRF/GATA4 signaling, GPCRs, class A rhodopsin-like, and p38 MAPK signaling pathway were related to downregulated genes. Finally, we predicted 39 probable effective drugs/agents for HE. This study not only confirms main important involved mechanisms of HE but also reveals some yet unknown activated molecular and cellular pathways in human HE. In addition, new targets were identified that could be of value in the future study of HE.
Keywords	Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Glymphatic System May Play a Vital Role in the Pathogenesis of Hepatic Encephalopathy

Ali Sepehrinezhad / Fin Stolze Larsen / Rezan Ashayeri Ahmadabad / Ali Shahbazi / Sajad Sahab Negah

Cells, Vol 12, Iss 979, p

A Narrative Review

2023 Volume 979

Abstract: Hepatic encephalopathy (HE) is a neurological complication of liver disease resulting in cognitive, psychiatric, and motor symptoms. Although hyperammonemia is a key factor in the pathogenesis of HE, several other factors have recently been discovered. ... ...

Abstract	Hepatic encephalopathy (HE) is a neurological complication of liver disease resulting in cognitive, psychiatric, and motor symptoms. Although hyperammonemia is a key factor in the pathogenesis of HE, several other factors have recently been discovered. Among these, the impairment of a highly organized perivascular network known as the glymphatic pathway seems to be involved in the progression of some neurological complications due to the accumulation of misfolded proteins and waste substances in the brain interstitial fluids (ISF). The glymphatic system plays an important role in the clearance of brain metabolic derivatives and prevents aggregation of neurotoxic agents in the brain ISF. Impairment of it will result in aggravated accumulation of neurotoxic agents in the brain ISF. This could also be the case in patients with liver failure complicated by HE. Indeed, accumulation of some metabolic by-products and agents such as ammonia, glutamine, glutamate, and aromatic amino acids has been reported in the human brain ISF using microdialysis technique is attributed to worsening of HE and correlates with brain edema. Furthermore, it has been reported that the glymphatic system is impaired in the olfactory bulb, prefrontal cortex, and hippocampus in an experimental model of HE. In this review, we discuss different factors that may affect the function of the glymphatic pathways and how these changes may be involved in HE.
Keywords	glymphatic system ; hepatic encephalopathy ; astrocytes ; brain fluids ; waste substances ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Computational-Based Drug Repurposing Method Targeting SARS-CoV-2 and its Neurological Manifestations Genes and Signaling Pathways

Ali Sepehrinezhad / Fariborz Rezaeitalab / Ali Shahbazi / Sajad Sahab-Negah

Bioinformatics and Biology Insights, Vol

2021 Volume 15

Abstract: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a global concern involves infections in multiple organs. Much of the research up to now has been descriptive on neurological manifestations ... ...

Abstract	Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a global concern involves infections in multiple organs. Much of the research up to now has been descriptive on neurological manifestations followed by SARS-CoV-2 infection. Despite considerable efforts on effective SARS-CoV-2 vaccine, novel therapeutic options for COVID-19 comorbidities are warranted. One of the fast ways to introduce possible effective drugs for clinical trials is bioinformatics methods. We have conducted a comprehensive enrichment analysis of genes involved in SARS-CoV-2 and neurological disorders associated with COVID-19. For this purpose, gene sets were extracted from the GeneWeaver database. To find out some significant enriched findings for common genes between SARS-CoV-2 and its neurological disorders, several practical databases were used. Finally, to repurpose an efficient drug, DrugBank databases were used. Overall, we detected 139 common genes concerning SARS-CoV-2 and their neurological disorders. Interestingly, our study predicted around 6 existing drugs (ie, carvedilol, andrographolide, 2-methoxyestradiol, etanercept, polaprezinc, and arsenic trioxide) that can be used for repurposing. We found that polaprezinc (zinc l -carnosine) drug is not investigated in the context of COVID-19 till now and it could be used for the treatment of COVID-19 and its neurological manifestations. To summarize, enrichment and network data get us a coherent picture to predict drug repurposing to speed up clinical trials.
Keywords	Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Neural stem cell therapy in conjunction with curcumin loaded in niosomal nanoparticles enhanced recovery from traumatic brain injury

Abdolreza Narouiepour / Alireza Ebrahimzadeh-bideskan / Ghadir Rajabzadeh / Ali Gorji / Sajad Sahab Negah

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 13

Abstract: Abstract Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI). Recently, stem cell therapy has emerged as a new avenue to address neuronal regeneration after TBI. However, the environment of TBI ... ...

Abstract	Abstract Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI). Recently, stem cell therapy has emerged as a new avenue to address neuronal regeneration after TBI. However, the environment of TBI lesions exerts negative effects on the stem cells efficacy. Therefore, to maximize the beneficial effects of stem cells in the course of TBI, we evaluated the effect of human neural stem/progenitor cells (hNS/PCs) and curcumin-loaded niosome nanoparticles (CM-NPs) on behavioral changes, brain edema, gliosis, and inflammatory responses in a rat model of TBI. After TBI, hNS/PCs were transplanted within the injury site and CM-NPs were orally administered for 10 days. Finally, the effect of combination therapy was compared to several control groups. Our results indicated a significant improvement of general locomotor activity in the hNS/PCs + CM-NPs treatment group compared to the control groups. We also observed a significant improvement in brain edema in the hNS/PCs + CM-NPs treatment group compared to the other groups. Furthermore, a significant decrease in astrogliosis was seen in the combined treatment group. Moreover, TLR4-, NF-κB-, and TNF-α- positive cells were significantly decreased in hNS/PCs + CM-NPs group compared to the control groups. Taken together, this study indicated that combination therapy of stem cells with CM-NPs can be an effective therapy for TBI.
Keywords	Medicine ; R ; Science ; Q
Subject code	150
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive–Compulsive Disorder

Ali Sepehrinezhad / Ali Shahbazi / Ali Bozorgmehr / Babak Kateb / Vicky Yamamoto / Sajad Sahab Negah

Journal of Personalized Medicine, Vol 12, Iss 7, p

2022 Volume 1043

Abstract: Background: There are no data available on the levels of genetic networks between obsessive–compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to ... ...

Abstract	Background: There are no data available on the levels of genetic networks between obsessive–compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to find novel genes that may be involved in the pathogenesis of OCD in MS. Methods: To obtain gene–gene interactions for MS and OCD, the STRING database was used. Cytoscape was then used to reconstruct and visualize graphs. Then, ToppGene and Enrichr were used to identify the main pathological processes and pathways involved in MS-OCD novel genes. Additionally, to predict transcription factors and microRNAs (miRNAs), the Enrichr database and miRDB database were used, respectively. Results: Our bioinformatics analysis showed that the signal transducer and the activator of transcription 3 ( STAT3 ) and neurotrophic receptor tyrosine kinase 2 ( NTRK2 ) genes had connections with 32 shared genes between MS and OCD. Furthermore, STAT3 and NTRK2 had the greatest enrichment parameters (i.e., molecular function, cellular components, and signaling pathways) among ten hub genes. Conclusions: To summarize, data from our bioinformatics analysis showed that there was a significant overlap in the genetic components of MS and OCD. The findings from this study make two contributions to future studies. First, predicted mechanisms related to STAT3 and NTRK2 in the context of MS and OCD can be investigated for pharmacological interventions. Second, predicted miRNAs related to STAT3 and NTRK2 can be tested as biomarkers in MS with OCD comorbidity. However, our study involved bioinformatics research; therefore, considerable experimental work (e.g., postmortem studies, case–control studies, and cohort studies) will need to be conducted to determine the etiology of OCD in MS from a mechanistic view.
Keywords	multiple sclerosis ; obsessive–compulsive disorder ; computational biology ; molecular function ; signaling pathway ; microRNAs ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Management And Support of Health Elites

Javad Momeni / Mohammad Mahdi Alvandi Fard / Parisa Qayenipour / Matin Ezzatabadipour / Elham Hosseini / Fatemeh Beiraghdar / Sajad Sahab Negah

Journal of Mazandaran University of Medical Sciences, Vol 33, Iss 2, Pp 411-

Opportunities, Challenges and Solutions

2023 Volume 428

Abstract: The issue of elites can be investigated in different political, cultural, economic, social, and sociological dimensions. In this context, the phenomenon of elite migration (brain drain) is one of the most important issues and problems of developing ... ...

Abstract	The issue of elites can be investigated in different political, cultural, economic, social, and sociological dimensions. In this context, the phenomenon of elite migration (brain drain) is one of the most important issues and problems of developing countries, especially Iran. The purpose of this study was to investigate solutions and find appropriate policies to improve conditions and deal with the challenges of the elites. Despite the decisions made and the work done regarding the elites, we are facing many challenges in the elitism. It is better to suggest institutions to identify the best talents and elites of the country from a younger age. With respect to the migration of the elites, it is imperative to prevent the exodus of the elites without their eventual return by implementing appropriate policies and acknowledging the contributions of the elites within the country. Additionally, we must harness the expertise of the migrated elites to mitigate the negative impact of migration on the economy. The portion of elite immigration has an inverse relationship with the gross domestic product (GDP) index, and for every 1 percent increase in elite immigration, GDP will decrease by 5.7 percent. Cooperation between different public and private sectors with the participation of elite society should be strengthened and solutions should be provided to facilitate their participation in the development of the country. Elites in health systems play important roles in improving health ecosystem. for this reason, special attention of the most important cases mentioned in this study.
Keywords	brain drain ; elites ; opportunities ; threats ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	300
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Mazandaran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Natural Cinnamaldehyde and Its Derivatives Ameliorate Neuroinflammatory Pathways in Neurodegenerative Diseases

Mehrdad Hajinejad / Maryam Ghaddaripouri / Maryam Dabzadeh / Fatemeh Forouzanfar / Sajad Sahab-Negah

BioMed Research International, Vol

2020 Volume 2020

Abstract: Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are conducted on the effects of natural products and their active components on ... ...

Abstract	Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are conducted on the effects of natural products and their active components on neurodegenerative diseases. This review will discuss an herbal constituent known as cinnamaldehyde (CA) with the neuroprotective potential to treat neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Accumulating evidence supports the notion that CA displays neuroprotective effects in AD and PD animal models by modulating neuroinflammation, suppressing oxidative stress, and improving the synaptic connection. CA exerts these effects through its action on multiple signaling pathways, including TLR4/NF-κB, NLRP3, ERK1/2-MEK, NO, and Nrf2 pathways. To summarize, CA and its derivatives have been shown to improve pathological changes in AD and PD animal models, which may provide a new therapeutic option for neurodegenerative interventions. To this end, further experimental and clinical studies are required to prove the neuroprotective effects of CA and its derivatives.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Safety and efficacy of bone marrow derived-mesenchymal stem cells transplantation in patients with amyotrophic lateral sclerosis

Jalil Tavakol-Afshari / Amir Reza Boroumand / Najmeh Kaffash Farkhad / Amir Adhami Moghadam / Sajad Sahab-Negah / Ali Gorji

Regenerative Therapy, Vol 18, Iss , Pp 268-

2021 Volume 274

Abstract: Stem cell-based treatments have emerged as potentially effective approaches to delay the progression of amyotrophic lateral sclerosis (ALS). This study was designed as a single-center, prospective, and open-label study without a placebo control group to ... ...

Abstract	Stem cell-based treatments have emerged as potentially effective approaches to delay the progression of amyotrophic lateral sclerosis (ALS). This study was designed as a single-center, prospective, and open-label study without a placebo control group to assess the safety and efficacy of concurrent intrathecal (IT) and intravenous (IV) administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS. Autologous BM-MSCs were isolated and expanded under standard conditions. Fifteen patients were neurologically examined before BM-MSCs transplantation (1 × 10 6 cells/kg BW) to evaluate the rate of pre-treatment disease progression. To assess the safety and efficacy, patients were examined at 1, 3, and 6 months following the treatment with BM-MSCs. Adverse reactions were assessed, and the clinical outcome was determined by the evaluation of the ALS functional rating scale-revised (ALSFRS-R) and forced vital capacity (FVC). No serious adverse reaction was observed after combined IT and IV administration of BM-MSCs. The mean ALSFRS-R and FVC values remained stable during the first 3 months of the treatment. However, a significant reduction in ALSFRS-R and FVC levels was observed in these patients 6 months after BM-MSCs administration. Our study revealed that the concurrent IT and IV application of BM-MSCs in patients with ALS is a safe procedure. Furthermore, our data indicate a temporary delay in the progression of ALS after a single combined IT and IV administration of BM-MSCs. Further studies are required to explore if the repeated applications of BM-MSCs could prolong survival and delay the progression of ALS.
Keywords	Stem cell therapy ; Clinical trial ; Amyotrophic lateral sclerosis ; Medicine (General) ; R5-920 ; Cytology ; QH573-671
Subject code	610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Study protocol

Roqayeh Aliyari / Sepideh Mahdavi / Mostafa Enayatrad / Sajad Sahab-Negah / Sairan Nili / Mohammad Fereidooni / Parvin Mangolian shahrbabaki / Alireza Ansari-Moghaddam / Abtin Heidarzadeh / Fariba Shahraki-Sanavi / Mohammadreza Amini Moridani / Mansooreh Fateh / Hamidreza Khajeha / Zahra Emamian / Elahe Behmanesh / Hamid Sharifi / Mohammad Hassan Emamian

BMC Public Health, Vol 22, Iss 1, Pp 1-

cohort event monitoring for safety signal detection after vaccination with COVID-19 vaccines in Iran

2022 Volume 7

Abstract: Abstract Background New vaccines that are initially approved in clinical trials are not completely free of risks. Systematic vaccine safety surveillance is required for ensuring safety of vaccines. This study aimed to provide a protocol for safety ... ...

Abstract	Abstract Background New vaccines that are initially approved in clinical trials are not completely free of risks. Systematic vaccine safety surveillance is required for ensuring safety of vaccines. This study aimed to provide a protocol for safety monitoring of COVID-19 vaccines, including Sputnik V, Sinopharm (BBIBP-CorV), COVIran Barekat, and AZD1222. Methods This is a prospective cohort study in accordance with a template provided by the World Health Organization. The target population includes citizens of seven cities in Iran who have received one of the available COVID-19 vaccines according to the national instruction on vaccination. The participants are followed for three months after they receive the second dose of the vaccine. For each type of vaccine, 30,000 people will be enrolled in the study of whom the first 1,000 participants are in the reactogenicity subgroup. The reactogenicity outcomes will be followed seven days after vaccination. Any hospitalization, COVID-19 disease, or other minor outcomes will be investigated in weekly follow-ups. The data are gathered through self-reporting of participants in a mobile application or phone calls to them. The study outcomes may be investigated for the third and fourth doses of vaccines. Other long-term outcomes may also be investigated after the expansion of the follow-up period. We have planned to complete data collection for the current objectives by the end 2022. Discussion The results of this study will be published in different articles. A live dashboard is also available for managers and policymakers. All data will be available on reasonable requests from the corresponding author.The use of the good and comprehensive guidelines provided by WHO, along with the accurate implementation of the protocol and continuous monitoring of the staff performance are the main strengths of this study which may be very useful for policymaking about COVID-19 vaccination.
Keywords	Cohort profile ; COVID-19 vaccine ; Iran ; Vaccination ; Safety ; Public aspects of medicine ; RA1-1270
Subject code	380
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antitumor Effects of 5-Aminolevulinic Acid on Human Malignant Glioblastoma Cells

Mohammad Jalili-Nik / Farzaneh Abbasinezhad-moud / Sajad Sahab-Negah / Abolfazl Maghrouni / Mohammad Etezad Razavi / Maryam Khaleghi Ghadiri / Walter Stummer / Ali Gorji

International Journal of Molecular Sciences, Vol 22, Iss 5596, p

2021 Volume 5596

Abstract: 5-Aminolevulinic acid (5-ALA) is a naturally occurring non-proteinogenic amino acid, which contributes to the diagnosis and therapeutic approaches of various cancers, including glioblastoma (GBM). In the present study, we aimed to investigate whether 5- ... ...

Abstract	5-Aminolevulinic acid (5-ALA) is a naturally occurring non-proteinogenic amino acid, which contributes to the diagnosis and therapeutic approaches of various cancers, including glioblastoma (GBM). In the present study, we aimed to investigate whether 5-ALA exerted cytotoxic effects on GBM cells. We assessed cell viability, apoptosis rate, mRNA expressions of various apoptosis-related genes, generation of reactive oxygen species (ROS), and migration ability of the human U-87 malignant GBM cell line (U87MG) treated with 5-ALA at different doses. The half-maximal inhibitory concentration of 5-ALA on U87MG cells was 500 μg/mL after 7 days; 5-ALA was not toxic for human optic cells and NIH-3T3 cells at this concentration. The application of 5-ALA led to a significant increase in apoptotic cells, enhancement of Bax and p53 expressions, reduction in Bcl-2 expression, and an increase in ROS generation. Furthermore, the application of 5-ALA increased the accumulation of U87MG cells in the SUB-G1 population, decreased the expression of cyclin D1, and reduced the migration ability of U87MG cells. Our data indicate the potential cytotoxic effects of 5-ALA on U87MG cells. Further studies are required to determine the spectrum of the antitumor activity of 5-ALA on GBM.
Keywords	brain tumor ; protoporphyrin ; cell death ; apoptosis ; tumor cell line ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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