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  1. Article ; Online: Increasing associations between defects in phospholipase C zeta and conditions of male infertility: not just ICSI failure?

    Kashir, Junaid

    Journal of assisted reproduction and genetics

    2020  Volume 37, Issue 6, Page(s) 1273–1293

    Abstract: Purpose: Oocyte activation is a fundamental event at mammalian fertilization. In mammals, this process is initiated by a series of characteristic calcium (Ca: Methods: An extensive literature search was performed using literature databases (PubMed/ ... ...

    Abstract Purpose: Oocyte activation is a fundamental event at mammalian fertilization. In mammals, this process is initiated by a series of characteristic calcium (Ca
    Methods: An extensive literature search was performed using literature databases (PubMed/MEDLINE/Web of Knowledge) focusing on phospholipase C zeta (PLCzeta; PLCζ), oocyte activation, and calcium oscillations, as well as specific male factor conditions.
    Results and discussion: Defective PLCζ or PLCζ-induced Ca
    Conclusions: Defective PLCζ and abnormal patterns of Ca
    MeSH term(s) Embryonic Development/genetics ; Female ; Fertilization/genetics ; Humans ; Infertility, Male/genetics ; Infertility, Male/pathology ; Male ; Oocytes/growth & development ; Oocytes/metabolism ; Phosphoinositide Phospholipase C/genetics ; Sperm Injections, Intracytoplasmic ; Sperm-Ovum Interactions/genetics ; Spermatozoa/metabolism ; Spermatozoa/pathology
    Chemical Substances PLCZ1 protein, human (EC 3.1.4.11) ; Phosphoinositide Phospholipase C (EC 3.1.4.11)
    Language English
    Publishing date 2020-04-14
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1112577-9
    ISSN 1573-7330 ; 1058-0468
    ISSN (online) 1573-7330
    ISSN 1058-0468
    DOI 10.1007/s10815-020-01748-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Editorial: The role of calcium signaling in gametogenesis and early embryogenesis.

    Kashir, Junaid / Lai, F Anthony / Nomikos, Michail

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 1051435

    Language English
    Publishing date 2022-10-11
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.1051435
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application.

    Kashir, Junaid / Ganesh, Durga / Jones, Celine / Coward, Kevin

    Human reproduction open

    2022  Volume 2022, Issue 2, Page(s) hoac003

    Abstract: Background: Oocyte activation deficiency (OAD) is attributed to the majority of cases underlying failure of ICSI cycles, the standard treatment for male factor infertility. Oocyte activation encompasses a series of concerted events, triggered by sperm- ... ...

    Abstract Background: Oocyte activation deficiency (OAD) is attributed to the majority of cases underlying failure of ICSI cycles, the standard treatment for male factor infertility. Oocyte activation encompasses a series of concerted events, triggered by sperm-specific phospholipase C zeta (PLCζ), which elicits increases in free cytoplasmic calcium (Ca
    Objective and rationale: Recent advances in current AOA techniques warrant a review of the safety and efficacy of these practices, to determine the extent to which AOA may be implemented in the clinic. Importantly, the primary challenges to obtaining data on the safety and efficacy of AOA must be determined. Such questions require urgent attention before widespread clinical utilization of such protocols can be advocated.
    Search methods: A literature review was performed using databases including PubMed, Web of Science, Medline, etc. using AOA, OAD, calcium ionophores, ICSI, PLCζ, oocyte activation, failed fertilization and fertilization failure as keywords. Relevant articles published until June 2019 were analysed and included in the review, with an emphasis on studies assessing large-scale efficacy and safety.
    Outcomes: Contradictory studies on the safety and efficacy of AOA do not yet allow for the establishment of AOA as standard practice in the clinic. Heterogeneity in study methodology, inconsistent sample inclusion criteria, non-standardized outcome assessments, restricted sample size and animal model limitations render AOA strictly experimental. The main scientific concern impeding AOA utilization in the clinic is the non-physiological method of Ca
    Limitations reasons for caution: The number of studies with clinical relevance using AOA remains significantly low. A much wider range of studies examining outcomes using multiple AOA agents are required.
    Wider implications: In addition to addressing the five main challenges of studies assessing AOA safety and efficacy, more standardized, large-scale, multi-centre studies of AOA, as well as long-term follow-up studies of children born from AOA, would provide evidence for establishing AOA as a treatment for infertility. The delivery of an activating agent that can more accurately recapitulate physiological fertilization, such as recombinant PLCζ, is a promising prospect for the future of AOA. Further to PLCζ, many other avenues of physiological oocyte activation also require urgent investigation to assess other potential physiological avenues of AOA.
    Study funding/competing interests: D.G. was supported by Stanford University's Bing Overseas Study Program. J.K. was supported by a Healthcare Research Fellowship Award (HF-14-16) made by Health and Care Research Wales (HCRW), alongside a National Science, Technology, and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST). The authors have no competing interests to declare.
    Language English
    Publishing date 2022-02-07
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2399-3529
    ISSN (online) 2399-3529
    DOI 10.1093/hropen/hoac003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19.

    Kashir, Junaid / Yaqinuddin, Ahmed

    Medical hypotheses

    2020  Volume 141, Page(s) 109786

    Abstract: Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation ... ...

    Abstract Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 h to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, ~100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times.
    MeSH term(s) Betacoronavirus/genetics ; Betacoronavirus/isolation & purification ; COVID-19 ; COVID-19 Testing ; COVID-19 Vaccines ; Clinical Laboratory Techniques/economics ; Clinical Laboratory Techniques/methods ; Coronavirus Infections/diagnosis ; Coronavirus Infections/economics ; Coronavirus Infections/virology ; DNA Primers ; Early Diagnosis ; Humans ; Molecular Diagnostic Techniques/economics ; Molecular Diagnostic Techniques/methods ; Nucleic Acid Amplification Techniques/economics ; Nucleic Acid Amplification Techniques/methods ; Pandemics/economics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/economics ; Pneumonia, Viral/virology ; RNA, Viral/analysis ; Real-Time Polymerase Chain Reaction/economics ; SARS-CoV-2 ; Sensitivity and Specificity ; Time Factors
    Chemical Substances COVID-19 Vaccines ; Covid-19 aAPC vaccine ; DNA Primers ; RNA, Viral
    Keywords covid19
    Language English
    Publishing date 2020-04-25
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2020.109786
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Novel therapeutic targets for SARS-CoV-2-induced acute lung injury: Targeting a potential IL-1β/neutrophil extracellular traps feedback loop.

    Yaqinuddin, Ahmed / Kashir, Junaid

    Medical hypotheses

    2020  Volume 143, Page(s) 109906

    Abstract: Most COVID-19 infected individuals present with mild flu-like symptoms; however, 5-10% of cases suffer from life-threatening pneumonia and respiratory failure. The pathogenesis of SARS-CoV-2 and its pathology of associated acute lung injury (ALI), acute ... ...

    Abstract Most COVID-19 infected individuals present with mild flu-like symptoms; however, 5-10% of cases suffer from life-threatening pneumonia and respiratory failure. The pathogenesis of SARS-CoV-2 and its pathology of associated acute lung injury (ALI), acute respiratory distress syndrome (ARDS), sepsis, coagulopathy and multiorgan failure is not known. SARS-CoV-2 is an envelope virus with S (spike), M (membrane), N (nucleocapsid) and E (envelop) proteins. In a closely related coronavirus (SARS-CoV), the transmembrane E protein exerts an important role in membrane-ionic transport through viroporins, deletion of which reduced levels of IL-1β and a remarkably reduced lung edema compared to wild type. IL-1β is generated by macrophages upon activation of intracellular NLRP3 (NOD-like, leucine rich repeat domains, and pyrin domain-containing protein 3), part of the functional NLRP3 inflammasome complex that detects pathogenic microorganisms and stressors, while neutrophils are enhanced by increasing levels of IL-1β. Expiring neutrophils undergo "NETosis", producing thread-like extracellular structures termed neutrophil extracellular traps (NETs), which protect against mild infections and microbes. However, uncontrolled NET production can cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), coagulopathy, multiple organ failure, and autoimmune disease. Herein, we present arguments underlying our hypothesis that IL-1β and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19. Considering such assertions, we propose potential drug candidates that could be used to alleviate such pathologies. Considering that recent efforts to ascertain effective treatments of COVID-19 in severe patients has been less than successful, investigating novel avenues of treating this virus are essential.
    MeSH term(s) Acute Lung Injury/drug therapy ; Acute Lung Injury/etiology ; Acute Lung Injury/immunology ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Extracellular Traps/drug effects ; Extracellular Traps/immunology ; Feedback, Physiological ; Humans ; Inflammasomes/immunology ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/immunology ; Models, Biological ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; SARS-CoV-2
    Chemical Substances Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human
    Keywords covid19
    Language English
    Publishing date 2020-05-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2020.109906
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents.

    Yaqinuddin, Ahmed / Kashir, Junaid

    Medical hypotheses

    2020  Volume 140, Page(s) 109777

    Abstract: Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate ...

    Abstract Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate an effective immune response against viruses, functional exhaustion of which enables disease progression. Patients with severe COVID-19 present significantly lower lymphocyte, and higher neutrophil, counts in blood. Specifically, CD8
    Keywords covid19
    Language English
    Publishing date 2020-04-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2020.109777
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Fertilization, Oocyte Activation, Calcium Release and Epigenetic Remodelling: Lessons From Cancer Models.

    Shafqat, Areez / Kashir, Junaid / Alsalameh, Sulaiman / Alkattan, Khaled / Yaqinuddin, Ahmed

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 781953

    Abstract: Oocyte activation deficiency (OAD) is the basis of Total Fertilisation Failure (TFF) and is attributed to mutations in the PLCζ gene-termed male factor infertility. This derives abnormal ... ...

    Abstract Oocyte activation deficiency (OAD) is the basis of Total Fertilisation Failure (TFF) and is attributed to mutations in the PLCζ gene-termed male factor infertility. This derives abnormal Ca
    Language English
    Publishing date 2022-03-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.781953
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Effect of SARS-CoV-2 Mutations on the Efficacy of Antibody Therapy and Response to Vaccines.

    Yaqinuddin, Ahmed / Shafqat, Areez / Kashir, Junaid / Alkattan, Khaled

    Vaccines

    2021  Volume 9, Issue 8

    Abstract: SARS-CoV-2 causes severe acute respiratory syndrome, which has led to significant morbidity and mortality around the world. Since its emergence, extensive prophylactic and therapeutic countermeasures have been employed to successfully prevent the spread ... ...

    Abstract SARS-CoV-2 causes severe acute respiratory syndrome, which has led to significant morbidity and mortality around the world. Since its emergence, extensive prophylactic and therapeutic countermeasures have been employed to successfully prevent the spread of COVID-19. Extensive work has been undertaken on using monoclonal antibody therapies, mass vaccination programs, and antiviral drugs to prevent and treat COVID-19. However, since antiviral drugs could take years to become widely available, immunotherapy and vaccines currently appear to be the most feasible option. In December 2020, the first vaccine against SARS-CoV-2 was approved by the World Health Organization (WHO) and, subsequently, many other vaccines were approved for use by different international regulators in different countries. Most monoclonal antibodies (mAbs) and vaccines target the SARS-CoV-2 surface spike (S) protein. Recently, mutant (or variant) SARS-CoV-2 strains with increased infectivity and virulence that evade protective host antibodies present either due to infection, antibody therapy, or vaccine administration have emerged. In this manuscript, we discuss the different monoclonal antibody and vaccine therapies available against COVID-19 and how the efficacy of these therapies is affected by the emergence of variants of SARS-CoV-2. We also discuss strategies that might help society cope with variants that could neutralize the effects of immunotherapy and escape the protective immunity conferred by vaccines.
    Language English
    Publishing date 2021-08-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines9080914
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: COVID-19: cross-immunity of viral epitopes may influence severity of infection and immune response.

    Kashir, Junaid / AlKattan, Khaled / Yaqinuddin, Ahmed

    Signal transduction and targeted therapy

    2021  Volume 6, Issue 1, Page(s) 102

    MeSH term(s) COVID-19 ; Cross Reactions ; Epitopes, B-Lymphocyte ; Humans ; Immunity ; SARS-CoV-2
    Chemical Substances Epitopes, B-Lymphocyte
    Language English
    Publishing date 2021-03-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2886872-9
    ISSN 2059-3635 ; 2095-9907
    ISSN (online) 2059-3635
    ISSN 2095-9907
    DOI 10.1038/s41392-021-00490-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: NET-Mediated Pathogenesis of COVID-19: The Role of NETs in Hepatic Manifestations

    Alkattan, Wael / Yaqinuddin, Ahmed / Shafqat, Areez / Kashir, Junaid

    Journal of Health and Allied Sciences NU

    2022  Volume 12, Issue 03, Page(s) 235–242

    Abstract: Some coronavirus disease-2019 (COVID-19) patients exhibit multi-organ failure, which often includes the liver. Indeed, liver disease appears to be an emerging feature of COVID-19 infections. However, the exact mechanism behind this remains unknown. ... ...

    Abstract Some coronavirus disease-2019 (COVID-19) patients exhibit multi-organ failure, which often includes the liver. Indeed, liver disease appears to be an emerging feature of COVID-19 infections. However, the exact mechanism behind this remains unknown. Neutrophil extracellular traps (NETs) have increasingly been attributed as major contributors to various liver pathologies, including sepsis, ischemic-reperfusion (I/R) injury, and portal hypertension in the setting of chronic liver disease. Although vital in normal immunity, excessive NET formation can drive inflammation, particularly of the endothelium. Collectively, we propose that NETs observed to be elevated in severe COVID-19 infection play principal roles in liver injury in addition to acute lung injury. Herein, we discuss the potential mechanisms underlying COVID-induced liver injury including cytopathic effects from direct liver infection, systemic inflammatory response syndrome, and hypoxic injury, encompassing I/R injury and coagulopathy. Further research is required to further elucidate the role of NETs in COVID. This holds potential therapeutic significance, as inhibition of NETosis could alleviate the symptoms of acute respiratory distress syndrome and liver injury, as well as other organs.
    Keywords COVID-19 ; SARS-CoV2 ; NETs ; liver disease ; ACE2 receptor ; multi-organ failure
    Language English
    Publishing date 2022-01-18
    Publisher Thieme Medical and Scientific Publishers Pvt. Ltd.
    Publishing place Stuttgart ; New York
    Document type Article
    ISSN 2582-4953 ; 2582-4287
    ISSN (online) 2582-4953
    ISSN 2582-4287
    DOI 10.1055/s-0041-1741418
    Database Thieme publisher's database

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