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Article ; Online: Cow's milk may be delivering potentially harmful undetected cargoes to humans. Is it time to reconsider dairy recommendations?

Wehbe, Zena / Kreydiyyeh, Sawsan

2021 Volume 80, Issue 4, Page(s) 874–888

Abstract: Mammalian evolution has shaped milk into a species-specific vehicle for post-natal development, continuing what began within the mother's womb. Increased consumption of the mother's breast milk is associated with the most adequate metabolic programming ... ...

Abstract	Mammalian evolution has shaped milk into a species-specific vehicle for post-natal development, continuing what began within the mother's womb. Increased consumption of the mother's breast milk is associated with the most adequate metabolic programming and lowers the incidence of the diseases of civilization during adulthood. An abundance of short sequences of RNA, known as microRNA, exists in mammalian breast milk, enclosed within robust small extracellular vesicles known as exosomes. These microRNAs can epigenetically regulate over 60% of human genes. When cow's milk is consumed by humans, the bovine exosomes are transported through the gastrointestinal tract, detected intact in the blood stream, and taken up by target cells, where they alter protein expression. The aim of this review was to highlight the role of dairy exosomes and microRNA, and of the type of dairy product consumed, in human diseases. Given that microRNAs are involved in a vast array of physiological processes and associated with several diseases, perhaps caution should be practiced with regard to human consumption of dairy, particularly for individuals within developmentally critical time frames, such as pregnant and lactating mothers, and young children.
MeSH term(s)	Animals ; Cattle ; Child, Preschool ; Exosomes ; Female ; Humans ; Lactation ; MicroRNAs/chemistry ; Milk/adverse effects ; Milk/chemistry ; Milk, Human/chemistry ; Pregnancy
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	82067-2
ISSN	1753-4887 ; 0029-6643
ISSN (online)	1753-4887
ISSN	0029-6643
DOI	10.1093/nutrit/nuab046
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Article ; Online: Key role for Kv11.1 (ether-a-go-go related gene) channels in rat bladder contractility.

Barrese, Vincenzo / Wehbe, Zena / Linden, Alice / McDowell, Sarah / Forrester, Elizabeth / Povstyan, Oleksander / McCloskey, Karen D / Greenwood, Iain A

Physiological reports

2023 Volume 11, Issue 3, Page(s) e15583

Abstract: In addition, to their established role in cardiac myocytes and neurons, ion channels encoded by ether-a-go-go-related genes (ERG1-3 or kcnh2,3 and 6) (kcnh2) are functionally relevant in phasic smooth muscle. The aim of the study was to determine the ... ...

Abstract	In addition, to their established role in cardiac myocytes and neurons, ion channels encoded by ether-a-go-go-related genes (ERG1-3 or kcnh2,3 and 6) (kcnh2) are functionally relevant in phasic smooth muscle. The aim of the study was to determine the expression and functional impact of ERG expression products in rat urinary bladder smooth muscle using quantitative polymerase chain reaction, immunocytochemistry, whole-cell patch-clamp and isometric tension recording. kcnh2 was expressed in rat bladder, whereas kcnh6 and kcnh3 expression were negligible. Immunofluorescence for the kcnh2 expression product Kv11.1 was detected in the membrane of isolated smooth muscle cells. Potassium currents with voltage-dependent characteristics consistent with Kv11.1 channels and sensitive to the specific blocker E4031 (1 μM) were recorded from isolated detrusor smooth muscles. Disabling Kv11.1 activity with specific blockers (E4031 and dofetilide, 0.2-20 μM) augmented spontaneous contractions to a greater extent than BK
MeSH term(s)	Rats ; Animals ; Urinary Bladder/metabolism ; Ether/metabolism ; Membrane Potentials/physiology ; Muscle, Smooth/metabolism ; Ethyl Ethers/metabolism ; Ethers/metabolism ; Nerve Tissue Proteins/metabolism ; Ether-A-Go-Go Potassium Channels/genetics ; Ether-A-Go-Go Potassium Channels/metabolism
Chemical Substances	Ether (0F5N573A2Y) ; Ethyl Ethers ; Ethers ; Kcnh3 protein, rat ; Nerve Tissue Proteins ; Ether-A-Go-Go Potassium Channels
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15583
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Article ; Online: Nano-targeting vascular remodeling in cancer: Recent developments and future directions.

Giordo, Roberta / Wehbe, Zena / Paliogiannis, Panagiotis / Eid, Ali H / Mangoni, Arduino A / Pintus, Gianfranco

Seminars in cancer biology

2022 Volume 86, Issue Pt 2, Page(s) 784–804

Abstract: Tumor growth and progression are strictly dependent on the adequate blood supply of oxygen and nutrients. The formation of new blood vessels and vascular networks is essential to ensure this demand. Blood vessels also facilitate the invasion of cancer ... ...

Abstract	Tumor growth and progression are strictly dependent on the adequate blood supply of oxygen and nutrients. The formation of new blood vessels and vascular networks is essential to ensure this demand. Blood vessels also facilitate the invasion of cancer cells into nearby tissues and their subsequent metastasis. Tumor cells represent the main driver of the neovascularization process through the direct or indirect, by neighboring non-cancer cells, release of pro-angiogenic molecules. The mediators (e.g., growth factors and extracellular matrix components), signaling pathways, cellular components, and processes (e.g., endothelial cell proliferation and migration) activated in tumor angiogenesis are similar to those involved in normal vascular development, except they lack efficient control mechanisms. Consequently, newly formed tumor vessels are typically fragile and hyperpermeable with a reduced and erratic blood flow. Targeting the tumor vasculature has been the focus of intense research over the last 20 years. However, despite the initial interest and expectations, the systemic use of anti-angiogenic drugs has not always led to therapeutic breakthroughs and, in some cases, has been associated with the development of tumor adaptive resistance resulting in a more aggressive phenotype. Therefore, new therapeutic approaches have focused on combining anti-angiogenic agents with chemotherapy or immunotherapy and/or optimizing (normalizing) the structure and function of tumor blood vessels to ensure a more efficient drug delivery. In this context, nanomedicine offers the significant advantage of targeting and releasing anti-angiogenic drugs at specific sites, minimizing toxicity in healthy tissues. Several nanoparticles possess intrinsic modulatory effects on angiogenesis, while others have been developed to facilitate drug delivery in association with chemotherapy, thermotherapy, radiotherapy or in response to specific stimuli within the tumor environment (e.g., enzymes, ions, redox potential) or exogenous stimuli (e.g., temperature, electricity, magnetic fields, and ultrasound). Other nanoparticles can modify, under specific conditions, their physical properties (e.g., dimensions, structure, and interactions) to increase penetration in tumor cells. This review provides a comprehensive appraisal of the critical modulators of tumor vascular biology, the most promising nano-strategies that specifically target such modulators, and the directions for future research and clinical applications.
MeSH term(s)	Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Remodeling ; Neoplasms/drug therapy ; Neoplasms/pathology ; Neovascularization, Pathologic/drug therapy ; Drug Delivery Systems
Chemical Substances	Angiogenesis Inhibitors
Language	English
Publishing date	2022-03-04
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2022.03.001
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Article: Disease-Associated Regulation of Non-Coding RNAs by Resveratrol: Molecular Insights and Therapeutic Applications.

Giordo, Roberta / Wehbe, Zena / Posadino, Anna Maria / Erre, Gian Luca / Eid, Ali H / Mangoni, Arduino A / Pintus, Gianfranco

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 894305

Abstract: There have been significant advances, particularly over the last 20 years, in the identification of non-coding RNAs (ncRNAs) and their pathophysiological role in a wide range of disease states, particularly cancer and other chronic conditions ... ...

Abstract	There have been significant advances, particularly over the last 20 years, in the identification of non-coding RNAs (ncRNAs) and their pathophysiological role in a wide range of disease states, particularly cancer and other chronic conditions characterized by excess inflammation and oxidative stress such as atherosclerosis, diabetes, obesity, multiple sclerosis, osteoporosis, liver and lung fibrosis. Such discoveries have potential therapeutic implications as a better understanding of the molecular mechanisms underpinning the effects of ncRNAs on critical homeostatic control mechanisms and biochemical pathways might lead to the identification of novel druggable targets. In this context, increasing evidence suggests that several natural compounds can target ncRNAs at different levels and, consequently, influence processes involved in the onset and progression of disease states. The natural phenol resveratrol has been extensively studied for therapeutic purposes in view of its established anti-inflammatory and antioxidant effects, particularly in disease states such as cancer and cardiovascular disease that are associated with human aging. However, increasing
Language	English
Publishing date	2022-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.894305
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Article ; Online: Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities.

Wehbe, Zena / Wehbe, Maya / Iratni, Rabah / Pintus, Gianfranco / Zaraket, Hassan / Yassine, Hadi M / Eid, Ali H

Frontiers in immunology

2021 Volume 12, Page(s) 663586

Abstract: As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and ... ...

Abstract	As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, have been approved for emergency use in various countries. However, the slow roll-out of vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. Moreover, vaccines are important tools for preventing the disease but therapeutic tools to treat patients are also needed. As such, since the beginning of the pandemic, repurposed FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to their known safety profiles and potential anti-viral effects. One of these drugs is ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral activity against various viruses including SARS-CoV-2. In this review, we delineate the story of how this antiparasitic drug was eventually identified as a potential treatment option for COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning points in past research that provided initial 'hints' for IVM's antiviral activity and its molecular mechanism of action- and finally, we culminate with the current clinical findings.
MeSH term(s)	Active Transport, Cell Nucleus/drug effects ; Animals ; Antiviral Agents/therapeutic use ; Cell Line ; Chlorocebus aethiops ; Coronavirus Nucleocapsid Proteins/antagonists & inhibitors ; Coronavirus Nucleocapsid Proteins/metabolism ; Drug Repositioning ; Humans ; Ivermectin/therapeutic use ; Phosphoproteins/antagonists & inhibitors ; Phosphoproteins/metabolism ; Protein Transport/drug effects ; SARS-CoV-2/drug effects ; SARS-CoV-2/growth & development ; Vero Cells ; Virus Replication/drug effects ; alpha Karyopherins/antagonists & inhibitors ; beta Karyopherins/antagonists & inhibitors ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Coronavirus Nucleocapsid Proteins ; Phosphoproteins ; alpha Karyopherins ; beta Karyopherins ; nucleocapsid phosphoprotein, SARS-CoV-2 ; Ivermectin (70288-86-7)
Language	English
Publishing date	2021-03-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.663586
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Article: Molecular Insights Into SARS COV-2 Interaction With Cardiovascular Disease: Role of RAAS and MAPK Signaling.

Wehbe, Zena / Hammoud, Safaa / Soudani, Nadia / Zaraket, Hassan / El-Yazbi, Ahmed / Eid, Ali H

Frontiers in pharmacology

2020 Volume 11, Page(s) 836

Abstract: In December 2019, reports of viral pneumonia came out of Wuhan city in Hubei province in China. In early 2020, the causative agent was identified as a novel coronavirus (CoV) sharing some sequence similarity with SARS-CoV that caused the severe acute ... ...

Abstract	In December 2019, reports of viral pneumonia came out of Wuhan city in Hubei province in China. In early 2020, the causative agent was identified as a novel coronavirus (CoV) sharing some sequence similarity with SARS-CoV that caused the severe acute respiratory syndrome outbreak in 2002. The new virus, named SARS-CoV-2, is highly contagious and spread rapidly across the globe causing a pandemic of what became known as coronavirus infectious disease 2019 (COVID-19). Early observations indicated that cardiovascular disease (CVD) patients are at higher risk of progression to severe respiratory manifestations of COVID-19 including acute respiratory distress syndrome. Moreover, further observations demonstrated that SARS-CoV-2 infection can induce
Keywords	covid19
Language	English
Publishing date	2020-06-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.00836
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Article ; Online: Estrogen and Bisphenol A in Hypertension.

Wehbe, Zena / Nasser, Suzanne A / El-Yazbi, Ahmed / Nasreddine, Salam / Eid, Ali H

Current hypertension reports

2020 Volume 22, Issue 3, Page(s) 23

Abstract: Purpose of review: Cardiovascular disease (CVD) is a non-subsiding disease that remains a leading cause of morbidity and mortality. CVD has been associated with endocrine disruptors, such as bisphenol A (BPA). This review critically summarizes existing ... ...

Abstract	Purpose of review: Cardiovascular disease (CVD) is a non-subsiding disease that remains a leading cause of morbidity and mortality. CVD has been associated with endocrine disruptors, such as bisphenol A (BPA). This review critically summarizes existing findings on BPA and hypertension, with particular attention to genomic, non-genomic, molecular, and cellular mechanisms of action that render BPA as a cardiovascular estrogenic disruptor. Recent findings: Owing to its similar estrogenic structure, BPA has been shown to affect various phenotypes that are regulated by the natural hormone, estrogen. Indeed, BPA has been shown to interact with estrogen receptors, located both in the cell membrane and in the cytoplasm/nucleus. Given that estrogen plays an important role in cardiovascular physiology, a contributing role for BPA in CVD would not be unexpected. Existing literature, though limited, established BPA as a source of disruption in cardiovascular health, particularly hypertension. However, effects of BPA are largely dependent on the dose, patient gender, tissue, and developmental stage of the exposed tissue/organ. Accumulating evidence argues for an adverse effect of BPA on blood pressure, with this effect being gender, dose, and time specific. Thus, comprehensive studies which take these factors and other parameters, like epigenetic factors, into account are warranted before a thorough understanding is at hand.
MeSH term(s)	Benzhydryl Compounds/adverse effects ; Estrogens/physiology ; Humans ; Hypertension/chemically induced ; Phenols/adverse effects
Chemical Substances	Benzhydryl Compounds ; Estrogens ; Phenols ; bisphenol A (MLT3645I99)
Language	English
Publishing date	2020-02-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-020-1022-z
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Zs.A 5522: Show issues

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Article ; Online: Molecular and Biological Mechanisms Underlying Gender Differences in COVID-19 Severity and Mortality.

Wehbe, Zena / Hammoud, Safaa Hisham / Yassine, Hadi M / Fardoun, Manal / El-Yazbi, Ahmed F / Eid, Ali H

Frontiers in immunology

2021 Volume 12, Page(s) 659339

Abstract: Globally, over two million people have perished due to the recent pandemic caused by SARS-CoV-2. The available epidemiological global data for SARS-CoV-2 portrays a higher rate of severity and mortality in males. Analyzing gender differences in the host ... ...

Abstract	Globally, over two million people have perished due to the recent pandemic caused by SARS-CoV-2. The available epidemiological global data for SARS-CoV-2 portrays a higher rate of severity and mortality in males. Analyzing gender differences in the host mechanisms involved in SARS-CoV-2 infection and progression may offer insight into the more detrimental disease prognosis and clinical outcome in males. Therefore, we outline sexual dimorphisms which exist in particular host factors and elaborate on how they may contribute to the pronounced severity in male COVID-19 patients. This includes disparities detected in comorbidities, the ACE2 receptor, renin-angiotensin system (RAS), signaling molecules involved in SARS-CoV-2 replication, proteases which prime viral S protein, the immune response, and behavioral considerations. Moreover, we discuss sexual disparities associated with other viruses and a possible gender-dependent response to SARS-CoV-2 vaccines. By specifically highlighting these immune-endocrine processes as well as behavioral factors that differentially exist between the genders, we aim to offer a better understanding in the variations of SARS-CoV-2 pathogenicity.
MeSH term(s)	Animals ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/mortality ; COVID-19 Vaccines/immunology ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/mortality ; Disease Progression ; Disease Susceptibility ; Female ; Humans ; Male ; Pandemics ; Renin-Angiotensin System ; Risk ; SARS-CoV-2/physiology ; Sex Characteristics ; Sex Factors
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2021-05-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.659339
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Article ; Online: An updated overview of cyanidins for chemoprevention and cancer therapy.

Posadino, Anna Maria / Giordo, Roberta / Ramli, Iman / Zayed, Hatem / Nasrallah, Gheyath K / Wehbe, Zena / Eid, Ali H / Gürer, Eda Sönmez / Kennedy, John F / Aldahish, Afaf Ahmed / Calina, Daniela / Razis, Ahmad Faizal Abdull / Modu, Babagana / Habtemariam, Solomon / Sharifi-Rad, Javad / Pintus, Gianfranco / Cho, William C

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 163, Page(s) 114783

Abstract: Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant ... ...

Abstract	Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-β-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration.
MeSH term(s)	Humans ; Anthocyanins/pharmacology ; Anthocyanins/therapeutic use ; Phytotherapy ; Flavonoids/therapeutic use ; Phytochemicals/pharmacology ; Chemoprevention ; Neoplasms/drug therapy ; Neoplasms/prevention & control ; Plant Extracts/pharmacology
Chemical Substances	cyanidin (7732ZHU564) ; Anthocyanins ; Flavonoids ; Phytochemicals ; Plant Extracts
Language	English
Publishing date	2023-04-28
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.114783
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Article ; Online: Molecular Insights Into SARS COV-2 Interaction With Cardiovascular Disease

Zena Wehbe / Safaa Hammoud / Nadia Soudani / Hassan Zaraket / Ahmed El-Yazbi / Ali H. Eid

Frontiers in Pharmacology, Vol

Role of RAAS and MAPK Signaling

2020 Volume 11

Abstract	In December 2019, reports of viral pneumonia came out of Wuhan city in Hubei province in China. In early 2020, the causative agent was identified as a novel coronavirus (CoV) sharing some sequence similarity with SARS-CoV that caused the severe acute respiratory syndrome outbreak in 2002. The new virus, named SARS-CoV-2, is highly contagious and spread rapidly across the globe causing a pandemic of what became known as coronavirus infectious disease 2019 (COVID-19). Early observations indicated that cardiovascular disease (CVD) patients are at higher risk of progression to severe respiratory manifestations of COVID-19 including acute respiratory distress syndrome. Moreover, further observations demonstrated that SARS-CoV-2 infection can induce de novo cardiac and vascular damage in previously healthy individuals. Here, we offer an overview of the proposed molecular pathways shared by the pathogenesis of CVD and SARS-CoV infections in order to provide a mechanistic framework for the observed interrelation. We examine the crosstalk between the renin-angiotensin-aldosterone system and mitogen activated kinase pathways that potentially links cardiovascular predisposition and/or outcome to SARS-CoV-2 infection. Finally, we summarize the possible effect of currently available drugs with known cardiovascular benefit on these pathways and speculate on their potential utility in mitigating cardiovascular risk and morbidity in COVID-19 patients.
Keywords	severe COVID-19 ; cardiovascular burden ; signaling pathways ; RAAS ; MAPK signaling ; Therapeutics. Pharmacology ; RM1-950 ; covid19
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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