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  1. Article: New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets.

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

    Bioinformatics and biology insights

    2023  Volume 17, Page(s) 11779322231155068

    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.
    Language English
    Publishing date 2023-02-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2423808-9
    ISSN 1177-9322
    ISSN 1177-9322
    DOI 10.1177/11779322231155068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Disclosing common biological signatures and predicting new therapeutic targets in schizophrenia and obsessive-compulsive disorder by integrated bioinformatics analysis.

    Ghanbarzehi, Abdolhakim / Sepehrinezhad, Ali / Hashemi, Nazanin / Karimi, Minoo / Shahbazi, Ali

    BMC psychiatry

    2023  Volume 23, Issue 1, Page(s) 40

    Abstract: Schizophrenia (SCZ) is a severe mental illness mainly characterized by a number of psychiatric symptoms. Obsessive-compulsive disorder (OCD) is a long-lasting and devastating mental disorder. SCZ has high co-occurrence with OCD resulting in the emergence ...

    Abstract Schizophrenia (SCZ) is a severe mental illness mainly characterized by a number of psychiatric symptoms. Obsessive-compulsive disorder (OCD) is a long-lasting and devastating mental disorder. SCZ has high co-occurrence with OCD resulting in the emergence of a concept entitled "schizo-obsessive disorder" as a new specific clinical entity with more severe psychiatric symptoms. Many studies have been done on SCZ and OCD, but the common pathogenesis between them is not clear yet. Therefore, this study aimed to identify shared genetic basis, potential biomarkers and therapeutic targets between these two disorders. Gene sets were extracted from the Geneweaver and Harmonizome databases for each disorder. Interestingly, the combination of both sets revealed 89 common genes between SCZ and OCD, the most important of which were BDNF, SLC6A4, GAD1, HTR2A, GRIN2B, DRD2, SLC6A3, COMT, TH and DLG4. Then, we conducted a comprehensive bioinformatics analysis of the common genes. Receptor activity as the molecular functions, neuron projection and synapse as the cellular components as well as serotonergic synapse, dopaminergic synapse and alcoholism as the pathways were the most significant commonalities in enrichment analyses. In addition, transcription factor (TFs) analysis predicted significant TFs such as HMGA1, MAPK14, HINFP and TEAD2. Hsa-miR-3121-3p and hsa-miR-495-3p were the most important microRNAs (miRNAs) associated with both disorders. Finally, our study predicted 19 existing drugs (importantly, Haloperidol, Fluoxetine and Melatonin) that may have a potential influence on this co-occurrence. To summarize, this study may help us to better understand and handle the co-occurrence of SCZ and OCD by identifying potential biomarkers and therapeutic targets.
    MeSH term(s) Humans ; Haloperidol/therapeutic use ; MicroRNAs ; Obsessive-Compulsive Disorder/diagnosis ; Psychotic Disorders/complications ; Schizophrenia/drug therapy ; Schizophrenia/genetics ; Schizophrenia/complications ; Serotonin Plasma Membrane Transport Proteins
    Chemical Substances Haloperidol (J6292F8L3D) ; MicroRNAs ; Serotonin Plasma Membrane Transport Proteins
    Language English
    Publishing date 2023-01-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2050438-X
    ISSN 1471-244X ; 1471-244X
    ISSN (online) 1471-244X
    ISSN 1471-244X
    DOI 10.1186/s12888-023-04543-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Human Endometrial Regenerative Cells for Neurological Disorders: Hype or Hope?

    Momeni, Javad / Naserzadeh, Elnaz / Sepehrinezhad, Ali / Ashayeri Ahmadabad, Rezan / Sahab Negah, Sajad

    International journal of stem cells

    2024  

    Abstract: Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson's disease, ...

    Abstract Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson's disease, Alzheimer's disease, etc.) central nervous system disorders. So, researchers are looking for alternative therapeutic modalities to manage the disease's symptoms and stop it from worsening. Concerning disease-modifying capabilities, stem cell therapy has emerged as an expanding domain. Among different types of stem cells, human endometrial regenerative cells have excellent regenerative properties, making them suitable for regenerative medicine. They have the potential for self-renewal and differentiation into three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells (MSCs). ERCs can be isolated from endometrial biopsy and menstrual blood samples. However, there is no comprehensive evidence on the effects of ERCs on neurological disorders. Hence, we initially explore the traits of these specific stem cells in this analysis, followed by an emphasis on their therapeutic potential in treating neurological disorders.
    Language English
    Publishing date 2024-01-08
    Publishing country Korea (South)
    Document type Journal Article ; Review
    ZDB-ID 2914134-5
    ISSN 2005-5447 ; 2005-3606
    ISSN (online) 2005-5447
    ISSN 2005-3606
    DOI 10.15283/ijsc23091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Monkeypox virus from neurological complications to neuroinvasive properties: current status and future perspectives.

    Sepehrinezhad, Ali / Ashayeri Ahmadabad, Rezan / Sahab-Negah, Sajad

    Journal of neurology

    2022  Volume 270, Issue 1, Page(s) 101–108

    Abstract: Cases of monkeypox (MPV) are sharply rising around the world. While most efforts are being focused on the management of the first symptoms of monkeypox, such as cutaneous lesions and flu-like symptoms, the effect of the monkeypox virus (MPXV) on multiple ...

    Abstract Cases of monkeypox (MPV) are sharply rising around the world. While most efforts are being focused on the management of the first symptoms of monkeypox, such as cutaneous lesions and flu-like symptoms, the effect of the monkeypox virus (MPXV) on multiple organs still remains unclear. Recently, several neurological manifestations, such as headache, myalgia, malaise, fatigue, altered consciousness, agitation, anorexia, nausea, and vomiting, have been reported in patients with MPV. In addition, data from experimental studies have indicated that MPXV can gain access to the central nervous system (CNS) through the olfactory epithelium and infected circulatory monocytes/macrophages as two probable neuroinvasive mechanisms. Therefore, there are growing concerns about the long-term effect of MPXV on the CNS and subsequent neurological complications. This paper highlights the importance of the neuroinvasive potential of MPXV, coupled with neurological manifestations.
    MeSH term(s) Humans ; Monkeypox virus/physiology ; Mpox (monkeypox)/diagnosis ; Mpox (monkeypox)/pathology ; Nervous System Diseases
    Language English
    Publishing date 2022-08-21
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 187050-6
    ISSN 1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    ISSN (online) 1432-1459
    ISSN 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    DOI 10.1007/s00415-022-11339-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. 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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  6. Article ; Online: SARS-CoV-2 may trigger inflammasome and pyroptosis in the central nervous system: a mechanistic view of neurotropism.

    Sepehrinezhad, Ali / Gorji, Ali / Sahab Negah, Sajad

    Inflammopharmacology

    2021  Volume 29, Issue 4, Page(s) 1049–1059

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the central nervous system and cause several neurological manifestations. Data from cerebrospinal fluid analyses and postmortem samples have been shown that SARS-CoV-2 has ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the central nervous system and cause several neurological manifestations. Data from cerebrospinal fluid analyses and postmortem samples have been shown that SARS-CoV-2 has neuroinvasive properties. Therefore, ongoing studies have focused on mechanisms involved in neurotropism and neural injuries of SARS-CoV-2. The inflammasome is a part of the innate immune system that is responsible for the secretion and activation of several pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and interleukin-18. Since cytokine storm has been known as a major mechanism followed by SARS-CoV-2, inflammasome may trigger an inflammatory form of lytic programmed cell death (pyroptosis) following SARS-CoV-2 infection and contribute to associated neurological complications. We reviewed and discussed the possible role of inflammasome and its consequence pyroptosis following coronavirus infections as potential mechanisms of neurotropism by SARS-CoV-2. Further studies, particularly postmortem analysis of brain samples obtained from COVID-19 patients, can shed light on the possible role of the inflammasome in neurotropism of SARS-CoV-2.
    MeSH term(s) Brain/immunology ; Brain/metabolism ; COVID-19/immunology ; COVID-19/metabolism ; Central Nervous System/immunology ; Central Nervous System/metabolism ; Humans ; Inflammasomes/immunology ; Inflammasomes/metabolism ; Pyroptosis/physiology ; SARS-CoV-2/immunology ; SARS-CoV-2/metabolism
    Chemical Substances Inflammasomes
    Language English
    Publishing date 2021-07-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1080058-x
    ISSN 1568-5608 ; 0925-4692
    ISSN (online) 1568-5608
    ISSN 0925-4692
    DOI 10.1007/s10787-021-00845-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Glymphatic System May Play a Vital Role in the Pathogenesis of Hepatic Encephalopathy: A Narrative Review.

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

    Cells

    2023  Volume 12, Issue 7

    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.
    MeSH term(s) Humans ; Glymphatic System/metabolism ; Hepatic Encephalopathy/etiology ; Brain/metabolism ; Brain Edema/metabolism ; Prefrontal Cortex/metabolism
    Language English
    Publishing date 2023-03-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12070979
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Inhibition of autotaxin alleviates pathological features of hepatic encephalopathy at the level of gut-liver-brain axis: an experimental and bioinformatic study.

    Sepehrinezhad, Ali / Shahbazi, Ali / Joghataei, Mohammad Taghi / Larsen, Fin Stolze / Sahab Negah, Sajad

    Cell death & disease

    2023  Volume 14, Issue 8, Page(s) 490

    Abstract: There is accumulating evidence that the circulatory levels of autotaxin (ATX) and lysophosphatidic acid (LPA) are increased in patients with severe liver disease. However, the potential role of the ATX-LPA axis in hepatic encephalopathy (HE) remains ... ...

    Abstract There is accumulating evidence that the circulatory levels of autotaxin (ATX) and lysophosphatidic acid (LPA) are increased in patients with severe liver disease. However, the potential role of the ATX-LPA axis in hepatic encephalopathy (HE) remains unclear. Our study aimed to investigate the role of the ATX-LPA signaling pathway in mice with thioacetamide (TAA) induced acute HE. To show the role of the ATX-LPA axis in the context of HE, we first measured the involvement of ATX-LPA in the pathogenesis of TAA-induced acute HE. Then, we compared the potential effects of ATX inhibitor (HA130) on astrocyte responses at in vitro and gut-liver-brain axis at in vivo levels. The inflammatory chemokine (C-C motif) ligand 3 was significantly increased in the hyperammonemic condition and could be prevented by ATX inhibition in astrocytes at in vitro level. Further statistical tests revealed that plasma and tissue pro-inflammatory cytokines were inhibited by HA130 in mice. Furthermore, the stage of HE was significantly improved by HA130. The most surprising result was that HA130 alleviated immune infiltrating cells in the liver and intestine and decreased mucus-secreting cells in the intestine. Further analysis showed that the levels of liver enzymes in serum were significantly decreased in response to ATX inhibition. Surprisingly, our data indicated that HA130 could recover permeabilization of the blood-brain barrier, neuroinflammation, and recognition memory. Besides that, we found that the changes of Interleukin-1 (IL-1) and aquaporin-4 (AQP4) in HE might have a connection with the glymphatic system based on bioinformatics analyses. Taken together, our data showed that the ATX-LPA axis contributes to the pathogenesis of HE and that inhibition of ATX improves HE.
    MeSH term(s) Mice ; Animals ; Hepatic Encephalopathy ; Liver Diseases ; Brain
    Language English
    Publishing date 2023-08-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-023-06022-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive-Compulsive Disorder.

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

    Journal of personalized medicine

    2022  Volume 12, Issue 7

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-06-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662248-8
    ISSN 2075-4426
    ISSN 2075-4426
    DOI 10.3390/jpm12071043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats.

    Sepehrinezhad, Ali / Dehghanian, Amirreza / Rafati, Ali / Ketabchi, Farzaneh

    BMC cardiovascular disorders

    2020  Volume 20, Issue 1, Page(s) 13

    Abstract: Background: Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood- ... ...

    Abstract Background: Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases.
    Methods: Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O
    Results: Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group.
    Conclusion: Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.
    MeSH term(s) Anesthesia, General ; Animals ; Biomarkers/blood ; Blood Pressure ; Common Bile Duct/surgery ; Disease Models, Animal ; Estradiol/blood ; Female ; Hemodynamics ; Hepatopulmonary Syndrome/blood ; Hepatopulmonary Syndrome/pathology ; Hepatopulmonary Syndrome/physiopathology ; Hyperoxia/blood ; Hyperoxia/physiopathology ; Hypoxia/blood ; Hypoxia/physiopathology ; Ligation ; Liver/pathology ; Liver Diseases/blood ; Liver Diseases/pathology ; Liver Diseases/physiopathology ; Malondialdehyde/blood ; Nitric Oxide/blood ; Portal Vein/surgery ; Pulmonary Circulation ; Rats, Sprague-Dawley ; Respiration, Artificial ; Severity of Illness Index ; Ventricular Function, Right ; Ventricular Pressure
    Chemical Substances Biomarkers ; Nitric Oxide (31C4KY9ESH) ; Estradiol (4TI98Z838E) ; Malondialdehyde (4Y8F71G49Q)
    Language English
    Publishing date 2020-01-13
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2059859-2
    ISSN 1471-2261 ; 1471-2261
    ISSN (online) 1471-2261
    ISSN 1471-2261
    DOI 10.1186/s12872-019-01297-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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