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  1. Article ; Online: Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.

    Mahmoud, Ismail Sami / Jarrar, Yazun Bashir / Febrimarsa

    Clinical and experimental medicine

    2023  Volume 23, Issue 6, Page(s) 2909–2923

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic coronavirus disease 2019 (COVID-19). Dysregulated and excessive production of cytokines and chemokines, known as cytokine storm, is frequently seen in ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic coronavirus disease 2019 (COVID-19). Dysregulated and excessive production of cytokines and chemokines, known as cytokine storm, is frequently seen in patients with severe COVID-19 disease and it can provoke a severe systematic inflammation in the patients. The IL-1R/TLRs/IRAKs signaling network is a key pathway in immune cells that plays a central role in regulating innate immunity and inflammatory responses via stimulating the expression and production of various proinflammatory molecules including cytokines. Modulation of IRAKs activity has been proposed to be a promising strategy in the treatment of inflammatory disorders. In this review, we highlight the biochemical properties of IRAKs and their role in regulating inflammatory molecular signaling pathways and discuss the potential targeting of IRAKs to suppress the SARS-CoV-2-induced cytokine storm in COVID-19 patients.
    MeSH term(s) Humans ; COVID-19 ; Cytokine Release Syndrome/drug therapy ; Cytokines ; Immunity, Innate ; SARS-CoV-2
    Chemical Substances Cytokines
    Language English
    Publishing date 2023-04-15
    Publishing country Italy
    Document type Journal Article ; Review
    ZDB-ID 2053018-3
    ISSN 1591-9528 ; 1591-8890
    ISSN (online) 1591-9528
    ISSN 1591-8890
    DOI 10.1007/s10238-023-01064-7
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    Zs.A 5481: Show issues Location:
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  2. Article ; Online: Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges.

    Mahmoud, Ismail Sami / Jarrar, Yazun Bashir

    Molecular biology reports

    2021  Volume 48, Issue 5, Page(s) 4667–4675

    Abstract: The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, ...

    Abstract The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, metastasis and viral infections. Recent studies have shown that TMPRSS2 expressed on cell surface of host cells could play a crucial role in activation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein which facilitates the rapid early entry of the virus into host cells. In addition, direct suppression of TMPRSS2 using small drug inhibitors has been demonstrated to be effective in decreasing SARS-CoV-2 infection in vitro, which presents TMPRSS2 protease as a potential therapeutic strategy for SARS-CoV-2 infection. Recently, SARS-CoV-2 has been shown to be capable of infecting gastrointestinal enterocytes and to provoke gastrointestinal disorders in patients with COVID-19 disease, which is considered as a new transmission route and target organ of SARS-CoV-2. In this review, we highlight the biochemical properties of TMPRSS2 protease and discuss the potential targeting of TMPRSS2 by inhibitors to prevent the SARS-CoV-2 spreading through gastro-intestinal tract system as well as the hurdles that need to be overcome.
    MeSH term(s) Antiviral Agents/pharmacology ; COVID-19/metabolism ; Drug Evaluation, Preclinical ; Enterocytes/drug effects ; Enterocytes/metabolism ; Enterocytes/virology ; Humans ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Serine Endopeptidases/metabolism ; Serine Proteinase Inhibitors/pharmacology ; Small Molecule Libraries/pharmacology ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization/drug effects ; COVID-19 Drug Treatment
    Chemical Substances Antiviral Agents ; Serine Proteinase Inhibitors ; Small Molecule Libraries ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
    Language English
    Publishing date 2021-05-22
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-021-06390-1
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  3. Article ; Online: Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications.

    Jarrar, Yazun Bashir / Lee, Su-Jun

    International journal of molecular sciences

    2019  Volume 20, Issue 17

    Abstract: Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of ...

    Abstract Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of
    MeSH term(s) Animals ; Cardiovascular Diseases/genetics ; Cytochrome P450 Family 4/genetics ; Humans ; Inflammation/genetics ; Linkage Disequilibrium ; Neoplasms/genetics ; Polymorphism, Genetic
    Chemical Substances Cytochrome P450 Family 4 (EC 1.14.14.1)
    Language English
    Publishing date 2019-08-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20174274
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  4. Article ; Online: The Nudix Hydrolase 15 (NUDT15) Gene Variants among Jordanian Arab Population

    Jarrar, Yazun Bashir / Ghishan, Maria

    Asian Pacific journal of cancer prevention : APJCP

    2019  Volume 20, Issue 3, Page(s) 801–808

    MeSH term(s) Adult ; Arabs/genetics ; Ethnic Groups/genetics ; Exons ; Female ; Genetic Variation ; Genetics, Population ; Genotype ; Humans ; Male ; Pyrophosphatases/genetics
    Chemical Substances NUDT15 protein, human (EC 2.6.1.-) ; Pyrophosphatases (EC 3.6.1.-)
    Language English
    Publishing date 2019-03-26
    Publishing country Thailand
    Document type Journal Article
    ZDB-ID 2218955-5
    ISSN 2476-762X ; 1513-7368
    ISSN (online) 2476-762X
    ISSN 1513-7368
    DOI 10.31557/APJCP.2019.20.3.801
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  5. Article ; Online: Maternal separation influences hepatic drug-metabolizing CYP450 gene expression without pathological changes in adult mice.

    Jarrar, Yazun Bashir / Ashour, Walaa' / Madani, Abdalla / Jarrar, Qais / Abulebdah, Dina / Jamous, Yahya F / Labban, Samah Y / Tazkarji, Mariam

    Journal of basic and clinical physiology and pharmacology

    2024  Volume 35, Issue 1-2, Page(s) 85–91

    Abstract: Objectives: The principal motive of this study is to explore the influence maternal separation (MS) exhibits on the mRNA expression of major drug metabolizing-cyp450s in parallel with the assessment of pathological changes that can be induced by MS in ... ...

    Abstract Objectives: The principal motive of this study is to explore the influence maternal separation (MS) exhibits on the mRNA expression of major drug metabolizing-cyp450s in parallel with the assessment of pathological changes that can be induced by MS in the livers of experimental mice.
    Methods: Eighteen
    Results: The study demonstrated that MS markedly downregulated (p<0.05) the mRNA expression of all tested drug-metabolizing cyp450s in livers of female and male mice. Furthermore, the mRNA levels of major drug-metabolizing cyp450s were notably lower (p<0.05) in livers of female MS mice as compared with male MS mice. It was found that values of the total body weight and liver weight of MS mice did not vary significantly (p>0.05) from those of the control groups. Additionally, histological examination revealed that the hepatic tissue of MS mice was normal, similar to that of the control mice.
    Conclusions: In summary, MS downregulates the gene expression of major hepatic drug-metabolizing cyp450s without inducing pathological alterations in the livers of mice. These findings provide an explanation for the heterogeneity in pharmacokinetics and drug response of patients with early life stress.
    MeSH term(s) Humans ; Adult ; Male ; Mice ; Female ; Animals ; Maternal Deprivation ; Cytochrome P-450 Enzyme System/genetics ; Liver/metabolism ; Mice, Inbred BALB C ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Gene Expression
    Chemical Substances Cytochrome P-450 Enzyme System (9035-51-2) ; RNA, Messenger
    Language English
    Publishing date 2024-03-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1071737-7
    ISSN 2191-0286 ; 0792-6855 ; 0334-1534
    ISSN (online) 2191-0286
    ISSN 0792-6855 ; 0334-1534
    DOI 10.1515/jbcpp-2023-0250
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3207: Show issues Location:
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  6. Article: Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

    Mahmoud, Ismail Sami / Jarrar, Yazun Bashir

    Molecular biology reports. 2021 May, v. 48, no. 5

    2021  

    Abstract: The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, ...

    Abstract The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, metastasis and viral infections. Recent studies have shown that TMPRSS2 expressed on cell surface of host cells could play a crucial role in activation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein which facilitates the rapid early entry of the virus into host cells. In addition, direct suppression of TMPRSS2 using small drug inhibitors has been demonstrated to be effective in decreasing SARS-CoV-2 infection in vitro, which presents TMPRSS2 protease as a potential therapeutic strategy for SARS-CoV-2 infection. Recently, SARS-CoV-2 has been shown to be capable of infecting gastrointestinal enterocytes and to provoke gastrointestinal disorders in patients with COVID-19 disease, which is considered as a new transmission route and target organ of SARS-CoV-2. In this review, we highlight the biochemical properties of TMPRSS2 protease and discuss the potential targeting of TMPRSS2 by inhibitors to prevent the SARS-CoV-2 spreading through gastro-intestinal tract system as well as the hurdles that need to be overcome.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; digestive tract ; drugs ; enterocytes ; metastasis ; molecular biology ; neoplasms ; proteinases ; serine ; therapeutics ; viruses
    Language English
    Dates of publication 2021-05
    Size p. 4667-4675.
    Publishing place Springer Netherlands
    Document type Article
    Note Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-021-06390-1
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  7. Article ; Online: Identification and functional characterization of CYP4V2 genetic variants exhibiting decreased activity of lauric acid metabolism.

    Jarrar, Yazun Bashir / Shin, Jae-Gook / Lee, Su-Jun

    Annals of human genetics

    2020  Volume 84, Issue 5, Page(s) 400–411

    Abstract: The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. ... ...

    Abstract The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein-coding variants were studied, including three novel variants (L22V, R287T, and G410C) and three previously reported variants (R36S, Q259K, and H331P). The cDNA sequences encoding each amino acid variant and the wild-type CYP4V2 protein were cloned into the pcDNA/PDEST40 expression vector and transfected into eukaryotic 293T cells for overexpression of the CYP4V2 coding variants. CYP4V2 H331P and CYP4V2 G410C exhibited significant decreases in activity for lauric acid oxidation (20-30% of wild-type activity), when compared to the wildtype, which was correlated with low expression of CYP4V2 H331P and G410C substituted proteins. The other four CYP4V2 amino variants were comparable to wild-type CYP4V2 for lauric acid metabolism. The CYP4V2 H331P and G410C substitutions were predicted to cause a structural change through in silico analysis. In conclusion, the present study provides functional information about CYP4V2 genetic variants. These findings will be valuable for interpreting individual variations in phenotypes associated with CYP4V2 function in the clinical setting.
    MeSH term(s) Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group/genetics ; Cytochrome P450 Family 4/genetics ; Haplotypes ; Humans ; Lauric Acids/metabolism ; Linkage Disequilibrium ; Phenotype ; Polymorphism, Single Nucleotide ; Republic of Korea ; Young Adult
    Chemical Substances Lauric Acids ; lauric acid (1160N9NU9U) ; CYP4V2 protein, human (EC 1.14.13.-) ; Cytochrome P450 Family 4 (EC 1.14.14.1)
    Language English
    Publishing date 2020-05-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 333-5
    ISSN 1469-1809 ; 0003-4800
    ISSN (online) 1469-1809
    ISSN 0003-4800
    DOI 10.1111/ahg.12388
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  8. Article: Alteration of the Respiratory Microbiome in Hospitalized Patients with Asthma-COPD Overlap during and after an Exacerbation.

    Alsayed, Ahmad R / Abed, Anas / Jarrar, Yazun Bashir / Alshammari, Farhan / Alshammari, Bushra / Basheti, Iman A / Zihlif, Malek

    Journal of clinical medicine

    2023  Volume 12, Issue 6

    Abstract: The immediate aim of this study was to comparatively examine the bacterial respiratory microbiome of patients in a stable state and during an exacerbation of asthma-COPD (chronic obstructive pulmonary disease) overlap (ACO). This prospective ... ...

    Abstract The immediate aim of this study was to comparatively examine the bacterial respiratory microbiome of patients in a stable state and during an exacerbation of asthma-COPD (chronic obstructive pulmonary disease) overlap (ACO). This prospective observational study took place in Jordan between 1 September 2021 and 30 April 2022. Sputum samples from patients with recognized ACO were acquired within 48 h of the exacerbation onset and again at 3 weeks following the exacerbation. The next-generation sequencing Illumina MiSeq was employed and uncovered significantly high bacterial diversity in the sputa. The results showed a significant decrease in the taxonomic richness in the sputum samples collected during the exacerbation episodes compared with those collected from patients in a stable state (
    Language English
    Publishing date 2023-03-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm12062118
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  9. Article ; Online: SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention.

    Mahmoud, Ismail Sami / Jarrar, Yazun Bashir / Alshaer, Walhan / Ismail, Said

    Biochimie

    2020  Volume 175, Page(s) 93–98

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the much updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 infections.
    MeSH term(s) Betacoronavirus/metabolism ; Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/metabolism ; Coronavirus Infections/therapy ; Host-Pathogen Interactions/physiology ; Humans ; Pandemics ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/therapy ; SARS-CoV-2 ; Virus Internalization
    Keywords covid19
    Language English
    Publishing date 2020-05-29
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 120345-9
    ISSN 1638-6183 ; 0300-9084
    ISSN (online) 1638-6183
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2020.05.012
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  10. Article ; Online: Inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) glucuronidation by non-steroidal anti-inflammatory drugs in human liver microsomes and recombinant UDP-glucuronosyltransferase enzymes.

    Jarrar, Yazun Bashir / Kim, Dong Hyun / Lee, Su-Jun / Shin, Jae-Gook

    Prostaglandins, leukotrienes, and essential fatty acids

    2020  Volume 153, Page(s) 102055

    Abstract: 20-hydroxyeicosatetraenoic acid (20-HETE) is an arachidonic acid metabolite which is known to increase platelet aggregation and cardiovascular risk. In this study, nine non-steroidal anti-inflammatory drugs (NSAIDs) selected by chemical structures were ... ...

    Abstract 20-hydroxyeicosatetraenoic acid (20-HETE) is an arachidonic acid metabolite which is known to increase platelet aggregation and cardiovascular risk. In this study, nine non-steroidal anti-inflammatory drugs (NSAIDs) selected by chemical structures were screened to determine their effects on the glucuronidation of 20-HETE using human liver microsomes (HLMs). Then, the combined effects of the selected NSAID and genetic polymorphisms in UDP-glucuronosyltransferase (UGT) were investigated. Among the tested NSAIDs, diclofenac was the strongest inhibitor of 20-HETE glucuronidation with an IC
    MeSH term(s) Adult ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Female ; Glucuronides/metabolism ; Glucuronosyltransferase/genetics ; Glucuronosyltransferase/metabolism ; Humans ; Hydroxyeicosatetraenoic Acids/chemistry ; Male ; Microsomes, Liver/chemistry ; Microsomes, Liver/drug effects ; Middle Aged ; Pharmacogenomic Variants ; Polymorphism, Single Nucleotide ; Republic of Korea ; Structure-Activity Relationship
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Glucuronides ; Hydroxyeicosatetraenoic Acids ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; UGT2B7 protein, human (EC 2.4.1.-) ; Glucuronosyltransferase (EC 2.4.1.17) ; UDP-glucuronosyltransferase 1A9 (EC 2.4.1.17)
    Language English
    Publishing date 2020-01-18
    Publishing country Scotland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 286714-x
    ISSN 1532-2823 ; 0952-3278
    ISSN (online) 1532-2823
    ISSN 0952-3278
    DOI 10.1016/j.plefa.2020.102055
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