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  1. Article: A novel approach to minimize the false negative COVID-19 diagnosis by inclusion of specific cell markers and multiple sample collection.

    Husain, Amjad

    MethodsX

    2021  Volume 8, Page(s) 101270

    Abstract: The SARS-CoV-2 pandemic has caused unpredictable mortality and economic losses globally. With no approved drug for the treatment, the accurate diagnosis of COVID-19 becomes essential. RNA based test takes several hours and require extensive human ... ...

    Abstract The SARS-CoV-2 pandemic has caused unpredictable mortality and economic losses globally. With no approved drug for the treatment, the accurate diagnosis of COVID-19 becomes essential. RNA based test takes several hours and require extensive human intervention for RNA extraction and RT-PCR, but it is preferred over the antibody-based detection as the latter does not detect the early stage infections. The RT-PCR being a gold standard of COVID-19 diagnosis offers highly standardized detection of the SARS-CoV-2 RNA, still vulnerable for false-negative diagnosis due to absence of infected cells in the sample or inaccurate RNA extraction. Hence there is a need to develop alternative protocols and methods for the accurate COVID-19 diagnosis. Here we propose two additional steps in RT-PCR based COVID-19 diagnosis to minimize false-negative detection. The first step involves collection of four samples from an individual. Each sample should be collected from nasopharyngeal and oropharyngeal regions on day 01, mixed together followed by RNA extraction and then repeating the same exercise on day 03. The RNA extracted on day 01 and day 03 must be pooled together to be used in the RT-PCR. Second, we propose the inclusion of the control marker genes specific to nasal goblet cell, type-II pneumocyte and absorptive enterocytes to ensure the specificity of the RNA source. Overall, these additional steps in the proposed method would increase the chances of SARS-CoV-2 detection in the infected population and would limit the false-negative diagnosis of COVID-19 and hence the spread of this disease.•RT-PCR based COVID-19 diagnosis is vulnerable to the false-negative results due to inaccurate sample isolation or RNA extraction.•RNA pool of multiple samples from an individual improves the chances of detection of SARS-CoV-2 by RT-PCR.•Inclusion of specific marker genes would ensure the right RNA source from the desired cell.
    Language English
    Publishing date 2021-02-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2830212-6
    ISSN 2215-0161
    ISSN 2215-0161
    DOI 10.1016/j.mex.2021.101270
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A novel approach to minimize the false negative COVID-19 diagnosis by inclusion of specific cell markers and multiple sample collection

    Ḥusain, Amjad

    MethodsX. 2021, v. 8 p.101270-

    2021  

    Abstract: The SARS-CoV-2 pandemic has caused unpredictable mortality and economic losses globally. With no approved drug for the treatment, the accurate diagnosis of COVID-19 becomes essential. RNA based test takes several hours and require extensive human ... ...

    Abstract The SARS-CoV-2 pandemic has caused unpredictable mortality and economic losses globally. With no approved drug for the treatment, the accurate diagnosis of COVID-19 becomes essential. RNA based test takes several hours and require extensive human intervention for RNA extraction and RT-PCR, but it is preferred over the antibody-based detection as the latter does not detect the early stage infections. The RT-PCR being a gold standard of COVID-19 diagnosis offers highly standardized detection of the SARS-CoV-2 RNA, still vulnerable for false-negative diagnosis due to absence of infected cells in the sample or inaccurate RNA extraction. Hence there is a need to develop alternative protocols and methods for the accurate COVID-19 diagnosis. Here we propose two additional steps in RT-PCR based COVID-19 diagnosis to minimize false-negative detection. The first step involves collection of four samples from an individual. Each sample should be collected from nasopharyngeal and oropharyngeal regions on day 01, mixed together followed by RNA extraction and then repeating the same exercise on day 03. The RNA extracted on day 01 and day 03 must be pooled together to be used in the RT-PCR. Second, we propose the inclusion of the control marker genes specific to nasal goblet cell, type-II pneumocyte and absorptive enterocytes to ensure the specificity of the RNA source. Overall, these additional steps in the proposed method would increase the chances of SARS-CoV-2 detection in the infected population and would limit the false-negative diagnosis of COVID-19 and hence the spread of this disease.•RT-PCR based COVID-19 diagnosis is vulnerable to the false-negative results due to inaccurate sample isolation or RNA extraction.•RNA pool of multiple samples from an individual improves the chances of detection of SARS-CoV-2 by RT-PCR.•Inclusion of specific marker genes would ensure the right RNA source from the desired cell.
    Keywords COVID-19 infection ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; drugs ; enterocytes ; exercise ; humans ; mortality ; nose ; pandemic ; pneumocytes ; A novel method to minimize the false negative COVID-19 diagnosis by inclusion of specific cell markers and multiple sample collection ; SARS-CoV-2 ; COVID-19 ; RT-PCR ; RdRp
    Language English
    Publishing place Elsevier B.V.
    Document type Article ; Online
    ZDB-ID 2830212-6
    ISSN 2215-0161
    ISSN 2215-0161
    DOI 10.1016/j.mex.2021.101270
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19.

    Husain, Amjad / Byrareddy, Siddappa N

    Chemico-biological interactions

    2020  Volume 331, Page(s) 109282

    Abstract: The novel human coronavirus-2 (HCoV-2), called SARS-CoV-2, is the causative agent of Coronavirus Induced Disease (COVID-19) and has spread causing a global pandemic. Currently, there is no vaccine to prevent infection nor any approved drug for the ... ...

    Abstract The novel human coronavirus-2 (HCoV-2), called SARS-CoV-2, is the causative agent of Coronavirus Induced Disease (COVID-19) and has spread causing a global pandemic. Currently, there is no vaccine to prevent infection nor any approved drug for the treatment. The development of a new drug is time-consuming and cannot be relied on as a solution in combatting the immediate global challenge. In such a situation, the drug repurposing becomes an attractive solution to identify the potential of COVID-19 treatment by existing drugs, which are approved for other indications. Here, we review the potential use of rapamycin, an mTOR (Mammalian Target of Rapamycin) inhibitor that can be repurposed at low dosages for the treatment of COVID-19. Rapamycin inhibits protein synthesis, delays aging, reduces obesity in animal models, and inhibits activities or expression of pro-inflammatory cytokines such as IL-2, IL-6 and, IL-10. Overall, the use of rapamycin can help to control viral particle synthesis, cytokine storms and contributes to fight the disease by its anti-aging and anti-obesity effects. Since, rapamycin targets the host factors and not viral machinery, it represents a potent candidate for the treatment of COVID-19 than antiviral drugs as its efficacy is less likely to be dampened with high mutation rate of viral RNA. Additionally, the inhibitory effect of rapamycin on cell proliferation may aid in reducing viral replication. Therefore, by drug repurposing, low dosages of rapamycin can be tested for the potential treatment of COVID-19/SARS-CoV-2 infection.
    MeSH term(s) Betacoronavirus/isolation & purification ; Betacoronavirus/physiology ; COVID-19 ; Cell Proliferation/drug effects ; Coronavirus Infections/drug therapy ; Coronavirus Infections/pathology ; Coronavirus Infections/virology ; Cytokines/metabolism ; Drug Repositioning ; Gene Expression/drug effects ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/pathology ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Sirolimus/pharmacology ; Sirolimus/therapeutic use ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism ; Virus Replication/drug effects
    Chemical Substances Cytokines ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Sirolimus (W36ZG6FT64)
    Keywords covid19
    Language English
    Publishing date 2020-10-06
    Publishing country Ireland
    Document type Journal Article ; Review
    ZDB-ID 218799-1
    ISSN 1872-7786 ; 0009-2797
    ISSN (online) 1872-7786
    ISSN 0009-2797
    DOI 10.1016/j.cbi.2020.109282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Targeting a transcription factor NF-κB by green tea catechins using

    Suhail, Mohd / Rehan, Mohd / Tarique, Mohammad / Tabrez, Shams / Husain, Amjad / Zughaibi, Torki A

    Frontiers in nutrition

    2023  Volume 9, Page(s) 1078642

    Abstract: Pancreatic cancer remains a lethal disease and a major public health problem globally. Nuclear factor-kappa B (NF-κB) has been identified as a therapeutic target in several cancers and plays an important role in inflammatory responses. Many ... ...

    Abstract Pancreatic cancer remains a lethal disease and a major public health problem globally. Nuclear factor-kappa B (NF-κB) has been identified as a therapeutic target in several cancers and plays an important role in inflammatory responses. Many phytochemicals, including catechins, have been reported in the scientific literature with efficient anticancer potential and minimal side effects. This study aims to gain insights into the inhibitory mechanism of catechin derivatives epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG) using
    Language English
    Publishing date 2023-01-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2022.1078642
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Aging and diabetes drive the COVID-19 forwards; unveiling nature and existing therapies for the treatment.

    Chawla, Udeep / Kashyap, Manoj Kumar / Husain, Amjad

    Molecular and cellular biochemistry

    2021  Volume 476, Issue 11, Page(s) 3911–3922

    Abstract: Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide and resulted in more than 3.5 million deaths so far. The infection causes Coronavirus disease (COVID-19) in people of all age groups, notably diabetic and old age ... ...

    Abstract Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide and resulted in more than 3.5 million deaths so far. The infection causes Coronavirus disease (COVID-19) in people of all age groups, notably diabetic and old age people, at a higher risk of infectivity and fatality. Around 35% of the patients who have died of the disease were diabetic. The infection is associated with weakening immune response, chronic inflammation, and potential direct pancreatic impairment. There seems to be a three-way association of the SARS-CoV-2 infection with diabetes and aging. The COVID-19 infection causes metabolism complications, which may induce diabetes and accelerate aging in healthy individuals. How does diabetes elevate the likelihood of the infection is not clearly understood. we summarize mechanisms of accelerated aging in COVID-19 and diabetes, and the possible correlation of these three diseases. Various drug candidates under different stages of pre-clinical or clinical developments give us hope for the development of COVID-19 therapeutics, but there is no approved drug so far to treat this disease. Here, we explored the potential of anti-diabetic and anti-aging natural compounds for the COVID-19 treatment. We have also reviewed different therapeutic strategies with plant-based natural products that may be used to cure patients infected with SARS-CoV-2 and post-infection syndrome.
    MeSH term(s) Age Factors ; Aging/drug effects ; Animals ; Antioxidants/therapeutic use ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/immunology ; Diabetes Mellitus/drug therapy ; Humans ; Hypoglycemic Agents/therapeutic use ; Pandemics ; Phytochemicals/therapeutic use ; SARS-CoV-2/physiology
    Chemical Substances Antioxidants ; Hypoglycemic Agents ; Phytochemicals
    Language English
    Publishing date 2021-06-24
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 184833-1
    ISSN 1573-4919 ; 0300-8177
    ISSN (online) 1573-4919
    ISSN 0300-8177
    DOI 10.1007/s11010-021-04200-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Substrate stiffening promotes VEGF-A functions via the PI3K/Akt/mTOR pathway

    Husain, Amjad / Khadka, Arogya / Ehrlicher, Allen / Saint-Geniez, Magali / Krishnan, Ramaswamy

    Biochemical and biophysical research communications. 2022 Jan. 01, v. 586

    2022  

    Abstract: While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR ... ...

    Abstract While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR signaling pathway. This pathway is activated on stiffer substrates, is amplified by VEGF-A stimulation, and correlates with enhanced endothelial cell (EC) proliferation, contraction, pro-angiogenic secretion, and capillary-like tube formation. In the settings of advanced age-related macular degeneration, characterized by EC and retinal pigment epithelial (RPE)-mediated angiogenesis, these data implicate substrate stiffness as a novel causative mechanism and Akt/mTOR inhibition as a novel therapeutic pathway.
    Keywords angiogenesis ; endothelial cells ; epithelium ; macular degeneration ; research ; secretion ; therapeutics ; vascular endothelial growth factor A
    Language English
    Dates of publication 2022-0101
    Size p. 27-33.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2021.11.030
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19

    Husain, Amjad / Byrareddy, Siddappa N

    Chem Biol Interact

    Abstract: The novel human coronavirus-2 (HCoV-2), called SARS-CoV-2, is the causative agent of Coronavirus Induced Disease (COVID-19) and has spread causing a global pandemic. Currently, there is no vaccine to prevent infection nor any approved drug for the ... ...

    Abstract The novel human coronavirus-2 (HCoV-2), called SARS-CoV-2, is the causative agent of Coronavirus Induced Disease (COVID-19) and has spread causing a global pandemic. Currently, there is no vaccine to prevent infection nor any approved drug for the treatment. The development of a new drug is time-consuming and cannot be relied on as a solution in combatting the immediate global challenge. In such a situation, the drug repurposing becomes an attractive solution to identify the potential of COVID-19 treatment by existing drugs, which are approved for other indications. Here, we review the potential use of rapamycin, an mTOR (Mammalian Target of Rapamycin) inhibitor that can be repurposed at low dosages for the treatment of COVID-19. Rapamycin inhibits protein synthesis, delays aging, reduces obesity in animal models, and inhibits activities or expression of pro-inflammatory cytokines such as IL-2, IL-6 and, IL-10. Overall, the use of rapamycin can help to control viral particle synthesis, cytokine storms and contributes to fight the disease by its anti-aging and anti-obesity effects. Since, rapamycin targets the host factors and not viral machinery, it represents a potent candidate for the treatment of COVID-19 than antiviral drugs as its efficacy is less likely to be dampened with high mutation rate of viral RNA. Additionally, the inhibitory effect of rapamycin on cell proliferation may aid in reducing viral replication. Therefore, by drug repurposing, low dosages of rapamycin can be tested for the potential treatment of COVID-19/SARS-CoV-2 infection.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #816316
    Database COVID19

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  8. Article ; Online: Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19

    Husain, Amjad / Byrareddy, Siddappa N.

    Chemico-Biological Interactions

    2020  Volume 331, Page(s) 109282

    Keywords Toxicology ; General Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 218799-1
    ISSN 1872-7786 ; 0009-2797
    ISSN (online) 1872-7786
    ISSN 0009-2797
    DOI 10.1016/j.cbi.2020.109282
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Substrate stiffening promotes VEGF-A functions via the PI3K/Akt/mTOR pathway.

    Husain, Amjad / Khadka, Arogya / Ehrlicher, Allen / Saint-Geniez, Magali / Krishnan, Ramaswamy

    Biochemical and biophysical research communications

    2021  Volume 586, Page(s) 27–33

    Abstract: While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR ... ...

    Abstract While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR signaling pathway. This pathway is activated on stiffer substrates, is amplified by VEGF-A stimulation, and correlates with enhanced endothelial cell (EC) proliferation, contraction, pro-angiogenic secretion, and capillary-like tube formation. In the settings of advanced age-related macular degeneration, characterized by EC and retinal pigment epithelial (RPE)-mediated angiogenesis, these data implicate substrate stiffness as a novel causative mechanism and Akt/mTOR inhibition as a novel therapeutic pathway.
    MeSH term(s) Biomechanical Phenomena ; Cell Line ; Cell Movement ; Cell Proliferation ; Elasticity ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Gene Expression Regulation ; Humans ; Mechanotransduction, Cellular/genetics ; Models, Biological ; Neovascularization, Pathologic/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Primary Cell Culture ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Retinal Pigment Epithelium/cytology ; Retinal Pigment Epithelium/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances VEGFA protein, human ; Vascular Endothelial Growth Factor A ; MTOR protein, human (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2021-11-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2021.11.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Discovery of a Novel Connecting Link between Renin-Angiotensin System and Cancer in Barrett's Esophagus by Proteomic Screening.

    Rao, Rashmi / Husain, Amjad / Bharti, Alok C / Kashyap, Manoj K

    Proteomics. Clinical applications

    2019  Volume 13, Issue 4, Page(s) e1900006

    Abstract: The renin-angiotensin system (RAS) plays a central role in the regulation of homeostasis and blood pressure. This involves an important enzyme called angiotensin-converting enzyme that leads to the conversion of angiotensin I into angiotensin II. RAS has ...

    Abstract The renin-angiotensin system (RAS) plays a central role in the regulation of homeostasis and blood pressure. This involves an important enzyme called angiotensin-converting enzyme that leads to the conversion of angiotensin I into angiotensin II. RAS has been reported to show association with inflammation, and in sporadic studies, with cancer. In particular, angiotensin II has been reported to be prevalent in the hypoxic microenvironment and associated with cancer signaling pathways. In a recent study, Bratlie et al. (Proteomics Clin. Appl. 2019, 4, 1800102) is shown to exploit 2D gel electrophoresis, and mass spectrometry (MS) to identify differentially expressed proteins by comparing low-grade dysplasia in Barrett's Esophagus (BE) following administration of agents that interfere with RAS, that is, enalapril and candesartan, and identified specific modulation of HSP60, PDIA3, and PPA1. Though 2D gel coupled with MS is a commonly-used tool for studying proteomes, it still has limitations in terms of a comprehensive analysis due to lack of absolute quantitation in a high-throughput manner. Despite technical limitations and the small size of the study, preliminary data emerging from the investigation show interference caused by clinically approved RAS inhibitors resulting in alteration of molecular markers associated with tumorigenicity. The authors propose potential factors that may influence the progression of the disease. However, these are conspicuous changes in high-abundance proteins only. Therefore, there is a need to carry out detailed experimental studies either using an in vitro labeling technique (isobaric labeling for relative and absolute quantitation) for tissues or an in vivo labeling technique (stable isotope labeling in animal cell culture) coupled with LC-MS/MS to identify differentially-regulated proteins to delineate the role of RAS in BE.
    MeSH term(s) Adenocarcinoma ; Angiotensin II ; Animals ; Barrett Esophagus ; Chromatography, Liquid ; Early Detection of Cancer ; Esophageal Neoplasms ; Proteomics ; Renin-Angiotensin System ; Tandem Mass Spectrometry ; Tumor Microenvironment
    Chemical Substances Angiotensin II (11128-99-7)
    Language English
    Publishing date 2019-04-14
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2261788-7
    ISSN 1862-8354 ; 1862-8346
    ISSN (online) 1862-8354
    ISSN 1862-8346
    DOI 10.1002/prca.201900006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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