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  1. Article: Targeting the Metabolic Paradigms in Cancer and Diabetes.

    Bosso, Mira / Haddad, Dania / Al Madhoun, Ashraf / Al-Mulla, Fahd

    Biomedicines

    2024  Volume 12, Issue 1

    Abstract: Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 ...

    Abstract Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the contrasting roles of oxidative phosphorylation (OXPHOS) and glycolysis as primary energy-generating pathways within cells. Building on earlier research, we explore how a shift towards one pathway over the other serves as a foundational aspect in the development of cancer and T2D. Unlike previous reviews, we posit that this shift may occur in seemingly opposing yet complementary directions, akin to the Yin and Yang concept. These metabolic fluctuations reveal an intricate network of underlying defective signaling pathways, orchestrating the pathogenesis and progression of each disease. The Warburg phenomenon, characterized by the prevalence of aerobic glycolysis over minimal to no OXPHOS, emerges as the predominant metabolic phenotype in cancer. Conversely, in T2D, the prevailing metabolic paradigm has traditionally been perceived in terms of discrete irregularities rather than an OXPHOS-to-glycolysis shift. Throughout T2D pathogenesis, OXPHOS remains consistently heightened due to chronic hyperglycemia or hyperinsulinemia. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, featuring differential tissue-specific alterations that affect OXPHOS. Recent findings suggest that addressing the metabolic imbalance in both cancer and diabetes could offer an effective treatment strategy. Numerous pharmaceutical and nutritional modalities exhibiting therapeutic effects in both conditions ultimately modulate the OXPHOS-glycolysis axis. Noteworthy nutritional adjuncts, such as alpha-lipoic acid, flavonoids, and glutamine, demonstrate the ability to reprogram metabolism, exerting anti-tumor and anti-diabetic effects. Similarly, pharmacological agents like metformin exhibit therapeutic efficacy in both T2D and cancer. This review discusses the molecular mechanisms underlying these metabolic shifts and explores promising therapeutic strategies aimed at reversing the metabolic imbalance in both disease scenarios.
    Language English
    Publishing date 2024-01-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines12010211
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  2. Article ; Online: Synthesis and structure-activity relationships of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives as 5-lipoxygenase inhibitors.

    Phillips, Oludotun A / Bosso, Mira A / Ezeamuzie, Charles I

    Journal of enzyme inhibition and medicinal chemistry

    2020  Volume 35, Issue 1, Page(s) 1471–1482

    Abstract: Oxazolidinone hydroxamic acid derivatives were synthesised and evaluated for inhibitory activity against leukotriene (LT) biosynthesis in ... ...

    Abstract Oxazolidinone hydroxamic acid derivatives were synthesised and evaluated for inhibitory activity against leukotriene (LT) biosynthesis in three
    MeSH term(s) Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Arachidonate 5-Lipoxygenase/metabolism ; Cell Line ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Humans ; Hydroxamic Acids/chemical synthesis ; Hydroxamic Acids/chemistry ; Hydroxamic Acids/pharmacology ; Inflammation/chemically induced ; Inflammation/drug therapy ; Inflammation/metabolism ; Leukotriene B4/antagonists & inhibitors ; Leukotriene B4/biosynthesis ; Lipoxygenase Inhibitors/chemical synthesis ; Lipoxygenase Inhibitors/chemistry ; Lipoxygenase Inhibitors/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Oxazolidinones/chemical synthesis ; Oxazolidinones/chemistry ; Oxazolidinones/pharmacology ; Structure-Activity Relationship ; Zymosan
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Hydroxamic Acids ; Lipoxygenase Inhibitors ; Oxazolidinones ; Leukotriene B4 (1HGW4DR56D) ; Zymosan (9010-72-4) ; Arachidonate 5-Lipoxygenase (EC 1.13.11.34)
    Language English
    Publishing date 2020-07-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2082578-X
    ISSN 1475-6374 ; 1475-6366
    ISSN (online) 1475-6374
    ISSN 1475-6366
    DOI 10.1080/14756366.2020.1786082
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  3. Article: The Two Faces of ACE2: The Role of ACE2 Receptor and Its Polymorphisms in Hypertension and COVID-19.

    Bosso, Mira / Thanaraj, Thangavel Alphonse / Abu-Farha, Mohamed / Alanbaei, Muath / Abubaker, Jehad / Al-Mulla, Fahd

    Molecular therapy. Methods & clinical development

    2020  Volume 18, Page(s) 321–327

    Abstract: The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. ACE2 is involved in ... ...

    Abstract The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. ACE2 is involved in modulating blood pressure and establishing blood pressure homeostasis. Recently, a critical debatable question has arisen whether using antihypertensive medications will have a favorable impact on people infected with SARS-CoV-2 or a deleterious one, mainly because angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-receptor blocker (ARB) therapy can modulate the expression of ACE2 protein. The concern is that the use of ACEIs and ARBs will increase the expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation. On the other hand, several genetic association studies have examined the relationship between ACE2 genetic variants and the risk of developing hypertension in different ethnic populations. In this review, we discuss the ongoing arguments in the literature about ACE2's role in mortality rate among coronavirus disease 2019 (COVID-19) patients comorbid with hypertension and critically evaluate the current debate about the usage or discontinuation of ACEI/ARB antihypertensive drugs. Moreover, we explore the two opposing roles that ACE2 genetic variants might be playing in COVID-19 by reducing ACE2 receptor effectiveness and mitigating SARS-CoV-2 infectivity.
    Keywords covid19
    Language English
    Publishing date 2020-06-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2020.06.017
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  4. Article ; Online: Whole genome amplification of DNA extracted from FFPE tissues.

    Bosso, Mira / Al-Mulla, Fahd

    Methods in molecular biology (Clifton, N.J.)

    2011  Volume 724, Page(s) 161–180

    Abstract: Whole genome amplification systems were developed to meet the increasing research demands on DNA resources and to avoid DNA shortage. The technology enables amplification of nanogram amounts of DNA into microgram quantities and is increasingly used in ... ...

    Abstract Whole genome amplification systems were developed to meet the increasing research demands on DNA resources and to avoid DNA shortage. The technology enables amplification of nanogram amounts of DNA into microgram quantities and is increasingly used in the amplification of DNA from multiple origins such as blood, fresh frozen tissue, formalin-fixed paraffin-embedded tissues, saliva, buccal swabs, bacteria, and plant and animal sources. This chapter focuses on the use of GenomePlex(®) tissue Whole Genome Amplification Kit, to amplify DNA directly from archived tissue. In addition, this chapter documents our unique experience with the utilization of GenomePlex(®) amplified DNA using several molecular techniques including metaphase Comparative Genomic Hybridization, array Comparative Genomic Hybridization, and real-time quantitative polymerase chain reaction assays. GenomePlex(®) is a registered trademark of Rubicon Genomics Incorporation.
    MeSH term(s) Alleles ; Comparative Genomic Hybridization ; DNA/isolation & purification ; Electrophoresis, Agar Gel ; Formaldehyde/chemistry ; Gene Dosage/genetics ; Genome, Human/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Microdissection ; Microscopy ; Paraffin Embedding/methods ; Polymerase Chain Reaction/methods ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results ; Tissue Extracts ; Tissue Fixation/methods
    Chemical Substances Tissue Extracts ; Formaldehyde (1HG84L3525) ; DNA (9007-49-2)
    Language English
    Publishing date 2011
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-61779-055-3_11
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  5. Article ; Online: The Two Faces of ACE2

    Mira Bosso / Thangavel Alphonse Thanaraj / Mohamed Abu-Farha / Muath Alanbaei / Jehad Abubaker / Fahd Al-Mulla

    Molecular Therapy: Methods & Clinical Development, Vol 18, Iss , Pp 321-

    The Role of ACE2 Receptor and Its Polymorphisms in Hypertension and COVID-19

    2020  Volume 327

    Abstract: The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. ACE2 is involved in ... ...

    Abstract The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. ACE2 is involved in modulating blood pressure and establishing blood pressure homeostasis. Recently, a critical debatable question has arisen whether using antihypertensive medications will have a favorable impact on people infected with SARS-CoV-2 or a deleterious one, mainly because angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-receptor blocker (ARB) therapy can modulate the expression of ACE2 protein. The concern is that the use of ACEIs and ARBs will increase the expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation. On the other hand, several genetic association studies have examined the relationship between ACE2 genetic variants and the risk of developing hypertension in different ethnic populations. In this review, we discuss the ongoing arguments in the literature about ACE2’s role in mortality rate among coronavirus disease 2019 (COVID-19) patients comorbid with hypertension and critically evaluate the current debate about the usage or discontinuation of ACEI/ARB antihypertensive drugs. Moreover, we explore the two opposing roles that ACE2 genetic variants might be playing in COVID-19 by reducing ACE2 receptor effectiveness and mitigating SARS-CoV-2 infectivity.
    Keywords ACE2 ; hypertension ; genetic variants ; angiotensin-renin system ; SARS-CoV-2 ; ACEI ; Genetics ; QH426-470 ; Cytology ; QH573-671 ; covid19
    Subject code 610
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
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  6. Article ; Online: The Two Faces of ACE2

    Bosso, Mira / Thanaraj, Thangavel Alphonse / Abu-Farha, Mohamed / Alanbaei, Muath / Abubaker, Jehad / Al-Mulla, Fahd

    Molecular Therapy - Methods & Clinical Development

    The Role of ACE2 Receptor and Its Polymorphisms in Hypertension and COVID-19

    2020  Volume 18, Page(s) 321–327

    Keywords covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2872938-9
    ISSN 2329-0501
    ISSN (online) 2329-0501
    DOI 10.1016/j.omtm.2020.06.017
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  7. Article: The Two Faces of ACE2: The Role of ACE2 Receptor and Its Polymorphisms in Hypertension and COVID-19

    Bosso, Mira / Thanaraj, Thangavel Alphonse / Abu-Farha, Mohamed / Alanbaei, Muath / Abubaker, Jehad / Al-Mulla, Fahd

    Mol. Ther. Methods Clin. Dev.

    Abstract: ... 19 by reducing ACE2 receptor effectiveness and mitigating SARS-CoV-2 infectivity.Bosso et al. discuss ...

    Abstract The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. ACE2 is involved in modulating blood pressure and establishing blood pressure homeostasis. Recently, a critical debatable question has arisen whether using antihypertensive medications will have a favorable impact on people infected with SARS-CoV-2 or a deleterious one, mainly because angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-receptor blocker (ARB) therapy can modulate the expression of ACE2 protein. The concern is that the use of ACEIs and ARBs will increase the expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation. On the other hand, several genetic association studies have examined the relationship between ACE2 genetic variants and the risk of developing hypertension in different ethnic populations. In this review, we discuss the ongoing arguments in the literature about ACE2's role in mortality rate among coronavirus disease 2019 (COVID-19) patients comorbid with hypertension and critically evaluate the current debate about the usage or discontinuation of ACEI/ARB antihypertensive drugs. Moreover, we explore the two opposing roles that ACE2 genetic variants might be playing in COVID-19 by reducing ACE2 receptor effectiveness and mitigating SARS-CoV-2 infectivity.Bosso et al. discuss the ongoing arguments about ACE2's role in the mortality associated with COVID-19 cases and weigh on the current debate about the usage or discontinuation of ACEI/ARB anti-hypertensive medication. They also explore the two opposing roles that ACE2 genetic variants might be playing in COVID-19.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #613810
    Database COVID19

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  8. Article ; Online: Effect of sleeve gastrectomy on the expression of meteorin-like (METRNL) and Irisin (FNDC5) in muscle and brown adipose tissue and its impact on uncoupling proteins in diet-induced obesity rats.

    Jamal, Mohammad H / Abu-Farha, Mohamed / Al-Khaledi, Ghanim / Al-Sabah, Suleiman / Ali, Hamad / Cherian, Preethi / Al-Khairi, Irina / AlOtaibi, Fatemah / Al-Ali, Waleed / Bosso, Mira / Dsouza, Carol / Abubaker, Jehad / Al-Mulla, Fahd

    Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery

    2020  Volume 16, Issue 12, Page(s) 1910–1918

    Abstract: Background: Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves ... ...

    Abstract Background: Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves metabolic homeostasis by modulating energy expenditure and enhancing thermogenesis through increasing the expression level of meteorin-like protein (METRNL) and fibronectin type III domain-containing protein 5 (FNDC5/Irisin) through uncoupling proteins 1/2/3 (UCP1, UCP2, and UCP3).
    Objectives: To study the effect of SG on the levels of proteins involved in thermogenesis process.
    Setting: Laboratory rats at Kuwait University.
    Methods: Male Sprague-Dawley rats, aged 4 to 5 weeks, were divided into 2 groups, control (n = 11) and diet-induced obesity (DIO) (n = 22). The control group was fed regular rat chow ad libitum, whereas the DIO group was fed cafeteria diet "high-fat/carbohydrate diet" ad libitum. At 21 weeks, rats in the DIO group that weighed 20% more than the control group animals underwent surgery. These rats were randomly subdivided into Sham and SG operation groups. Gene expression was evaluated, and enzyme-linked immunosorbent assays were employed to assess the changes in gene and protein levels in tissue and circulation.
    Results: The protein expression data revealed an increase in METRNL levels in the muscles and white adipose tissue of SG animals. METRNL level in circulation in SG animals was reduced compared with control and Sham rats. The level of Irisin increased in the muscle of SG animals compared with the control and Sham group animals; however, a decrease in Irisin level was observed in the white adipose tissue and brown adipose tissue of SG animals compared with controls. Gene expression analysis revealed decreased METRNL levels in muscle tissues in the SG group compared with the control group animals. Increased expression of FNDC5 (Irisin), UCP2, and UCP3 in the muscle tissue of SG animals was also observed. Furthermore, the levels of UCP1, UCP2, UCP3, and METRNL in the brown adipose tissue of SG animals were upregulated. No significant alteration in the gene expression of Irisin was observed in brown adipose tissue.
    Conclusions: Sleeve gastrectomy induces weight loss through complex mechanisms that may include browning of fat.
    MeSH term(s) Adipose Tissue/metabolism ; Adipose Tissue, Brown ; Animals ; Diet ; Fibronectins/genetics ; Fibronectins/metabolism ; Gastrectomy ; Kuwait ; Male ; Mitochondrial Uncoupling Proteins ; Muscles/metabolism ; Obesity/genetics ; Obesity/surgery ; Rats ; Rats, Sprague-Dawley
    Chemical Substances FNDC5 protein, rat ; Fibronectins ; Mitochondrial Uncoupling Proteins
    Language English
    Publishing date 2020-07-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2274243-8
    ISSN 1878-7533 ; 1550-7289
    ISSN (online) 1878-7533
    ISSN 1550-7289
    DOI 10.1016/j.soard.2020.07.022
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    Zs.A 6572: Show issues Location:
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  9. Article ; Online: Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study.

    Gordon, Jacob A / Buonerba, Carlo / Pond, Gregory / Crona, Daniel / Gillessen, Silke / Lucarelli, Giuseppe / Rossetti, Sabrina / Dorff, Tanya / Artale, Salvatore / Locke, Jennifer A / Bosso, Davide / Milowsky, Matthew Ivan / Witek, Mira Sofie / Battaglia, Michele / Pignata, Sandro / Cherhroudi, Cyrus / Cox, Michael E / De Placido, Pietro / Ribera, Dario /
    Omlin, Aurelius / Buonocore, Gaetano / Chi, Kim / Kollmannsberger, Christian / Khalaf, Daniel / Facchini, Gaetano / Sonpavde, Guru / De Placido, Sabino / Eigl, Bernhard J / Di Lorenzo, Giuseppe

    Oncotarget

    2018  Volume 9, Issue 28, Page(s) 19861–19873

    Abstract: Background: Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical ... ...

    Abstract Background: Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide.
    Materials and methods: This was a retrospective multicenter study including patients that received abiraterone or enzalutamide for mCRPC. The effect of concurrent statin use on outcomes was evaluated. The associations of statins with early (≤12 weeks) prostate-specific antigen (PSA) declines (> 30%), cancer-specific survival and overall survival (OS) were evaluated after controlling for known prognostic factors.
    Results: Five hundred and ninety-eight patients treated with second-line abiraterone or enzalutamide after docetaxel for mCRPC were included. A total of 199 men (33.3%) received statins during abiraterone/enzalutamide treatment. Median OS was 20.8 months (95% CI = 18.3-23.2) for patients who received statins, versus 12.9 months (95% CI = 11.4-14.6) for patients who did not receive statins (
    Conclusions: In this retrospective cohort, statin use was significantly associated with both prolonged OS and cancer-specific survival and increased early > 30% PSA declines. Prospective validation is warranted.
    Language English
    Publishing date 2018-04-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.24888
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