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Article ; Online: Satureja khuzistanica Jamzad essential oil and pure carvacrol attenuate TBI-induced inflammation and apoptosis via NF-κB and caspase-3 regulation in the male rat brain

Elham Abbasloo / Sedigheh Amiresmaili / Sara Shirazpour / Mohammad Khaksari / Firas Kobeissy / Theresa Currier Thomas

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 14

Abstract: Abstract Traumatic brain injury (TBI) causes progressive dysfunction that induces biochemical and metabolic changes that lead to cell death. Nevertheless, there is no definitive FDA-approved therapy for TBI treatment. Our previous immunohistochemical ... ...

Abstract	Abstract Traumatic brain injury (TBI) causes progressive dysfunction that induces biochemical and metabolic changes that lead to cell death. Nevertheless, there is no definitive FDA-approved therapy for TBI treatment. Our previous immunohistochemical results indicated that the cost-effective natural Iranian medicine, Satureja khuzistanica Jamzad essential oil (SKEO), which consists of 94.16% carvacrol (CAR), has beneficial effects such as reducing neuronal death and inflammatory markers, as well as activating astrocytes and improving neurological outcomes. However, the molecular mechanisms of these neuroprotective effects have not yet been elucidated. This study investigated the possible mechanisms involved in the anti-inflammatory and anti-apoptotic properties of SKEO and CAR after TBI induction. Eighty-four male Wistar rats were randomly divided into six groups: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg), and TBI + SKEO (200 mg/kg) groups. After establishing the “Marmarou” weight drop model, diffuse TBI was induced in the rat brain. Thirty minutes after TBI induction, SKEO & CAR were intraperitoneally injected. One day after TBI, injured rats exhibited significant brain edema, neurobehavioral dysfunctions, and neuronal apoptosis. Western blot results revealed upregulation of the levels of cleaved caspase-3, NFκB p65, and Bax/Bcl-2 ratio, which was attenuated by CAR and SKEO (200 mg/kg). Furthermore, the ELISA results showed that CAR treatment markedly prevents the overproduction of the brain pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Moreover, the neuron-specific enolase (NSE) immunohistochemistry results revealed the protective effect of CAR and SKEO on post-TBI neuronal death. The current study revealed that the possible neuroprotective mechanisms of SKEO and CAR might be related to (at least in part) modulating NF-κB regulated inflammation and caspase-3 protein expression. It also suggested that CAR exerts more potent protective effects than SKEO against TBI. ...
Keywords	Medicine ; R ; Science ; Q
Subject code	380 ; 610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Bioinformatics Systems Biology Analysis of the Current Oral Proteomic Biomarkers and Implications for Diagnosis and Treatment of External Root Resorption

Mahmoud Mona / Zunnaira Abbasi / Firas Kobeissy / Abdulrahman Chahbandar / Roberta Pileggi

International Journal of Molecular Sciences, Vol 22, Iss 3181, p

2021 Volume 3181

Abstract: External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic ... ...

Abstract	External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic disorders, or idiopathic causes. Often, if undiagnosed and untreated, ERR can lead to the loss of the tooth or multiple teeth. Traditionally, clinicians have relied on radiographs and cone beam computed tomography (CBCT) images for the diagnosis of ERR; however, these techniques are not often precise or definitive and may require exposure of patients to more ionizing radiation than necessary. To overcome these shortcomings, there is an immense need to develop non-invasive approaches such as biomarker screening methods for rapid and precise diagnosis for ERR. In this review, we performed a literature survey for potential salivary or gingival crevicular fluid (GCF) proteomic biomarkers associated with ERR and analyzed the potential pathways leading to ERR. To the best of our knowledge, this is the first proteomics biomarker survey that connects ERR to body biofluids which represents a novel approach to diagnose and even monitor treatment progress for ERR.
Keywords	external root resorption ; invasive cervical resorption ; dentin sialoprotein ; dentin phosphoproteins ; dentin sialophosphoprotein ; dentin matrix acidic phosphoprotein 1 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Antitumor Effect of the DNA Polymerase Alpha Inhibitor ST1926 in Glioblastoma

Chirine El-Baba / Zeinab Ayache / Mona Goli / Berthe Hayar / Zeinab Kawtharani / Claudio Pisano / Firas Kobeissy / Yehia Mechref / Nadine Darwiche

International Journal of Molecular Sciences, Vol 24, Iss 14069, p

A Proteomics Approach

2023 Volume 14069

Abstract: Glioblastoma Multiforme (GBM) is the most aggressive form of malignant brain tumor. The median survival rate does not exceed two years, indicating an imminent need to develop novel therapies. The atypical adamantyl retinoid ST1926 induces apoptosis and ... ...

Abstract	Glioblastoma Multiforme (GBM) is the most aggressive form of malignant brain tumor. The median survival rate does not exceed two years, indicating an imminent need to develop novel therapies. The atypical adamantyl retinoid ST1926 induces apoptosis and growth inhibition in different cancer types. We have shown that ST1926 is an inhibitor of the catalytic subunit of DNA polymerase alpha (POLA1), which is involved in initiating DNA synthesis in eukaryotic cells. POLA1 levels are elevated in GBM versus normal brain tissues. Therefore, we studied the antitumor effects of ST1926 in several human GBM cell lines. We further explored the global protein expression profiles in GBM cell lines using liquid chromatography coupled with tandem mass spectrometry to identify new targets of ST1926. Low sub-micromolar concentrations of ST1926 potently decreased cell viability, induced cell damage and apoptosis, and reduced POLA1 protein levels in GBM cells. The proteomics profiles revealed 197 proteins significantly differentially altered upon ST1926 treatment of GBM cells involved in various cellular processes. We explored the differential gene and protein expression of significantly altered proteins in GBM compared to normal brain tissues.
Keywords	glioblastoma ; ST1926 ; POLA1 inhibitor ; proteomics ; biomarkers ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Beirut Ammonium Nitrate Blast

Samar Al-Hajj / Hassan R. Dhaini / Stefania Mondello / Haytham Kaafarani / Firas Kobeissy / Ralph G. DePalma

Frontiers in Public Health, Vol

Analysis, Review, and Recommendations

2021 Volume 9

Abstract: A massive chemical detonation occurred on August 4, 2020 in the Port of Beirut, Lebanon. An uncontrolled fire in an adjacent warehouse ignited ~2,750 tons of Ammonium Nitrate (AN), producing one of the most devastating blasts in recent history. The blast ...

Abstract	A massive chemical detonation occurred on August 4, 2020 in the Port of Beirut, Lebanon. An uncontrolled fire in an adjacent warehouse ignited ~2,750 tons of Ammonium Nitrate (AN), producing one of the most devastating blasts in recent history. The blast supersonic pressure and heat wave claimed the lives of 220 people and injured more than 6,500 instantaneously, with severe damage to the nearby dense residential and commercial areas. This review represents one of the in-depth reports to provide a detailed analysis of the Beirut blast and its health and environmental implications. It further reviews prior AN incidents and suggests actionable recommendations and strategies to optimize chemical safety measures, improve emergency preparedness, and mitigate the delayed clinical effects of blast and toxic gas exposures. These recommended actionable steps offer a starting point for government officials and policymakers to build frameworks, adopt regulations, and implement chemical safety protocols to ensure safe storage of hazardous materials as well as reorganizing healthcare system disaster preparedness to improve emergency preparedness in response to similar large-scale disasters and promote population safety. Future clinical efforts should involve detailed assessment of physical injuries sustained by blast victims, with systemic mitigation and possible treatment of late blast effects involving individuals, communities and the region at large.
Keywords	ammonium nitrate explosion ; blast injury ; Beirut ; emergency preparedness ; health hazard ; traumatic brain injury ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mitoquinone Helps Combat the Neurological, Cognitive, and Molecular Consequences of Open Head Traumatic Brain Injury at Chronic Time Point

Muhammad Ali Haidar / Zaynab Shakkour / Chloe Barsa / Maha Tabet / Sarin Mekhjian / Hala Darwish / Mona Goli / Deborah Shear / Jignesh D. Pandya / Yehia Mechref / Riyad El Khoury / Kevin Wang / Firas Kobeissy

Biomedicines, Vol 10, Iss 250, p

2022 Volume 250

Abstract: Traumatic brain injury (TBI) is a heterogeneous disease in its origin, neuropathology, and prognosis, with no FDA-approved treatments. The pathology of TBI is complicated and not sufficiently understood, which is the reason why more than 30 clinical ... ...

Abstract	Traumatic brain injury (TBI) is a heterogeneous disease in its origin, neuropathology, and prognosis, with no FDA-approved treatments. The pathology of TBI is complicated and not sufficiently understood, which is the reason why more than 30 clinical trials in the past three decades turned out unsuccessful in phase III. The multifaceted pathophysiology of TBI involves a cascade of metabolic and molecular events including inflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. In this study, an open head TBI mouse model, induced by controlled cortical impact (CCI), was used to investigate the chronic protective effects of mitoquinone (MitoQ) administration 30 days post-injury. Neurological functions were assessed with the Garcia neuroscore, pole climbing, grip strength, and adhesive removal tests, whereas cognitive and behavioral functions were assessed using the object recognition, Morris water maze, and forced swim tests. As for molecular effects, immunofluorescence staining was conducted to investigate microgliosis, astrocytosis, neuronal cell count, and axonal integrity. The results show that MitoQ enhanced neurological and cognitive functions 30 days post-injury. MitoQ also decreased the activation of astrocytes and microglia, which was accompanied by improved axonal integrity and neuronal cell count in the cortex. Therefore, we conclude that MitoQ has neuroprotective effects in a moderate open head CCI mouse model by decreasing oxidative stress, neuroinflammation, and axonal injury.
Keywords	neurotrauma ; oxidative stress ; neurodegeneration ; neuroinflammation ; moderate traumatic brain injury ; Biology (General) ; QH301-705.5
Subject code	150
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients

Callum N. Watson / Ghazala Begum / Emma Ashman / Daniella Thorn / Kamal M. Yakoub / Moustafa Al Hariri / Ali Nehme / Stefania Mondello / Firas Kobeissy / Antonio Belli / Valentina Di Pietro

Cells, Vol 11, Iss 163, p

2022 Volume 163

Abstract: Alzheimer’s disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing ... ...

Abstract	Alzheimer’s disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls. The aim of the study was to identify in the late stage of AD, the key dysregulated pathways that may contribute to pathogenesis and then to evaluate whether any of these pathways could be detected in the early phase of AD, opening new opportunity for early treatment that could stop or delay the pathology. Six common pathways were found regulated by miRNAs and proteins in the late stage of AD, with one of them (Rap1 signalling) activated since the early phase. MiRNAs and proteins were also compared to explore an inverse trend of expression which could lead to the identification of new therapeutic targets. These results suggest that specific miRNA changes could represent molecular fingerprint of neurodegenerative processes and potential therapeutic targets for early intervention.
Keywords	Alzheimer’s disease ; microRNA profile ; protein profile ; co-expression analysis ; Rap1 signalling ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Advances in Cardiovascular Biomarker Discovery

Crystal M. Ghantous / Layla Kamareddine / Rima Farhat / Fouad A. Zouein / Stefania Mondello / Firas Kobeissy / Asad Zeidan

Biomedicines, Vol 8, Iss 552, p

2020 Volume 552

Abstract: Cardiovascular diseases are the leading causes of mortality worldwide. Among them, hypertension and its pathological complications pose a major risk for the development of other cardiovascular diseases, including heart failure and stroke. Identifying ... ...

Abstract	Cardiovascular diseases are the leading causes of mortality worldwide. Among them, hypertension and its pathological complications pose a major risk for the development of other cardiovascular diseases, including heart failure and stroke. Identifying novel and early stage biomarkers of hypertension and other cardiovascular diseases is of paramount importance in predicting and preventing the major morbidity and mortality associated with these diseases. Biomarkers of such diseases or predisposition to their development are identified by changes in a specific indicator’s expression between healthy individuals and patients. These include changes in protein and microRNA (miRNA) levels. Protein profiling using mass spectrometry and miRNA screening utilizing microarray and sequencing have facilitated the discovery of proteins and miRNA as biomarker candidates. In this review, we summarized some of the different, promising early stage protein and miRNA biomarker candidates as well as the currently used biomarkers for hypertension and other cardiovascular diseases. Although a number of promising markers have been identified, it is unlikely that a single biomarker will unambiguously aid in the classification of these diseases. A multi-marker panel-strategy appears useful and promising for classifying and refining risk stratification among patients with cardiovascular disease.
Keywords	biomarkers ; cardiovascular diseases ; hypertension ; proteomics ; miRNA ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Screening of tau protein kinase inhibitors in a tauopathy-relevant cell-based model of tau hyperphosphorylation and oligomerization.

Hamad Yadikar / Isabel Torres / Gabrielle Aiello / Milin Kurup / Zhihui Yang / Fan Lin / Firas Kobeissy / Richard Yost / Kevin K Wang

PLoS ONE, Vol 15, Iss 7, p e

2020 Volume 0224952

Abstract: Tauopathies are a class of neurodegenerative disorders characterized by abnormal deposition of post-translationally modified tau protein in the human brain. Tauopathies are associated with Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), ...

Abstract	Tauopathies are a class of neurodegenerative disorders characterized by abnormal deposition of post-translationally modified tau protein in the human brain. Tauopathies are associated with Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and other diseases. Hyperphosphorylation increases tau tendency to aggregate and form neurofibrillary tangles (NFT), a pathological hallmark of AD. In this study, okadaic acid (OA, 100 nM), a protein phosphatase 1/2A inhibitor, was treated for 24h in mouse neuroblastoma (N2a) and differentiated rat primary neuronal cortical cell cultures (CTX) to induce tau-hyperphosphorylation and oligomerization as a cell-based tauopathy model. Following the treatments, the effectiveness of different kinase inhibitors was assessed using the tauopathy-relevant tau antibodies through tau-immunoblotting, including the sites: pSer202/pThr205 (AT8), pThr181 (AT270), pSer202 (CP13), pSer396/pSer404 (PHF-1), and pThr231 (RZ3). OA-treated samples induced tau phosphorylation and oligomerization at all tested epitopes, forming a monomeric band (46-67 kDa) and oligomeric bands (170 kDa and 240 kDa). We found that TBB (a casein kinase II inhibitor), AR and LiCl (GSK-3 inhibitors), cyclosporin A (calcineurin inhibitor), and Saracatinib (Fyn kinase inhibitor) caused robust inhibition of OA-induced monomeric and oligomeric p-tau in both N2a and CTX culture. Additionally, a cyclin-dependent kinase 5 inhibitor (Roscovitine) and a calcium chelator (EGTA) showed contrasting results between the two neuronal cultures. This study provides a comprehensive view of potential drug candidates (TBB, CsA, AR, and Saracatinib), and their efficacy against tau hyperphosphorylation and oligomerization processes. These findings warrant further experimentation, possibly including animal models of tauopathies, which may provide a putative Neurotherapy for AD, CTE, and other forms of tauopathy-induced neurodegenerative diseases.
Keywords	Medicine ; R ; Science ; Q
Subject code	571 ; 572
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors

Mahmoud Mona / Firas Kobeissy / Yun-Jong Park / Rehae Miller / Wafaa Saleh / Jin Koh / Mi-Jeong Yoo / Sixue Chen / Seunghee Cha

International Journal of Molecular Sciences, Vol 21, Iss 9055, p

2020 Volume 9055

Abstract: Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative ... ...

Abstract	Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries.
Keywords	mouse bone marrow-derived stem cells (mMSC) ; co-culture ; secretome ; salivary glands ; Sjögren’s Syndrome ; salivary progenitors ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Epigenetic Studies Revealed a Ghost Proteome in PC1/3 KD Macrophages under Antitumoral Resistance Induced by IL-10

Tristan Cardon / Bilgehan Ozcan / Soulaimane Aboulouard / Firas Kobeissy / Marie Duhamel / Franck Rodet / Isabelle Fournier / Michel Salzet

ACS Omega, Vol 5, Iss 43, Pp 27774-

2020 Volume 27782

Keywords	Chemistry ; QD1-999
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	American Chemical Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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