Article
Public, Environmental & Occupational Health
Susana Cararo Confortin, Liliana Yanet Gomez Aristizabal, Elma Izze da Silva Magalhaes, Aline Rodrigues Barbosa, Cecilia Claudia Costa Ribeiro, Rosangela Fernandes Lucena Batista, Antonio Augusto Moura da Silva
Summary: There is no association between sleep duration and cardiometabolic risk factors in adolescents.
Article
Biochemistry & Molecular Biology
Carlota Oleaga, Joshua Hay, Emma Gurcan, Larry L. David, Paul A. Mueller, Hagai Tavori, Michael D. Shapiro, Nathalie Pamir, Sergio Fazio
Summary: Our study confirms that PCSK9_55 is predominantly formed extracellularly with a shorter half-life, while a small intracellular pool of PCSK9_55 remains non-secreted. Intracellularly retained PCSK9_55 exhibits reduced efficiency in inducing LDLR degradation compared to PCSK9_62.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Nutrition & Dietetics
Jacksaint Saintila, Laura E. Baquedano-Santana, Yaquelin E. Calizaya-Milla, Cristian Ramos-Vera, Antonio Serpa Barrientos, Renzo F. Carranza-Esteban
Summary: For university teachers, the frequency of breakfast consumption is associated with cardiometabolic risk. Skipping breakfast can have detrimental effects on cardiometabolic health. Promoting the benefits of breakfast is of great public health interest.
FRONTIERS IN NUTRITION
(2023)
Article
Medicine, Research & Experimental
Khadijeh Mahboobnia, Matteo Pirro, Ettore Marini, Francesco Grignani, Evgeny E. Bezsonov, Tannaz Jamialahmadi, Amirhossein Sahebkar
Summary: PCSK9 plays an important role in the development and progression of various cancers, highlighting its potential significance in cancer treatment. Inhibiting PCSK9 may help suppress the proliferation and invasion of tumor cells. However, the current lack of data on the role of PCSK9 in cancer and the impact of PCSK9 inhibition in cancer therapy limits our understanding of its effectiveness and safety.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Tadeja Sotler, Miran Sebestjen
Summary: Disturbances in lipid metabolism are a major risk factor for atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important protein in lipid metabolism that is also involved in inflammation, endothelial dysfunction, and atherosclerotic plaque development. PCSK9 has been linked to inflammation and plays a role in the initiation and development of atherosclerotic lesions. Experimental studies have shown that an increased concentration of PCSK9 accelerates endothelial cell apoptosis and impairs endothelial function, creating conditions for the development of atherosclerosis. PCSK9 inhibitors can improve clinical outcomes through both lipid-dependent and lipid-independent pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Kari A. Makela, Jari Jokelainen, Ville Stenback, Juha Auvinen, Marjo-Riitta Jarvelin, Mikko Tulppo, Juhani Leppaluoto, Sirkka Keinanen-Kiukaanniemi, Karl-Heinz Herzig
Summary: The study examined the effects of PCSK9 in patients with alterations of glucose metabolism and statin therapy, showing that in subjects with abnormal glucose metabolism and statin treatment, the significant PCSK9-mediated effects on lipid metabolites are diminished compared to those with normal glucose tolerance (NGT) subjects, although statins can reduce LDL-C and VLDL-C levels.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Carlota Oleaga, Michael D. Shapiro, Joshua Hay, Paul A. Mueller, Joshua Miles, Cecilia Huang, Emily Friz, Hagai Tavori, Peter P. Toth, Cezary Wojcik, Bruce A. Warden, Jonathan Q. Purnell, P. Barton Duell, Nathalie Pamir, Sergio Fazio
Summary: This study investigated the mechanisms behind the increase in plasma PCSK9 levels in response to PCSK9i therapy. The findings suggest that PCSK9i enhances PCSK9 secretion, contributing to the elevated plasma PCSK9 levels in treated subjects.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Sheila M. M. Manemann, Suzette J. J. Bielinski, Ethan D. D. Moser, Jennifer L. L. St Sauver, Paul Y. Y. Takahashi, Veronique L. Roger, Janet E. E. Olson, Alanna M. M. Chamberlain, Alan T. T. Remaley, Paul A. A. Decker, Jill M. M. Killian, Nicholas B. B. Larson
Summary: This study found that variability in lipid levels is associated with increased risk of cardiovascular disease (CVD) in a large electronic health record-based population cohort. High variability in total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol is independently associated with an increased risk of CVD.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Cell Biology
Peter Gennemark, Katrin Walter, Niclas Clemmensen, Dinko Rekic, Catarina A. M. Nilsson, Jane Knochel, Mikko Holtta, Linda Wernevik, Birgitta Rosengren, Dorota Kakol-Palm, Yanfeng Wang, Rosie Z. Yu, Richard S. Geary, Stan J. Riney, Brett P. Monia, Rikard Isaksson, Rasmus Jansson-Lofmark, Cristina S. J. Rocha, Daniel Linden, Eva Hurt-Camejo, Rosanne Crooke, Lloyd Tillman, Tina Ryden-Bergsten, Bjorn Carlsson, Ulf Andersson, Marie Elebring, Anna Tivesten, Nigel Davies
Summary: In this study, a chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery was developed and shown to effectively reduce LDL cholesterol levels. Animal experiments demonstrated liver targeting and significant reductions in PCSK9 and LDL cholesterol levels after oral administration.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Nurjannatul Naim Kamaruddin, Nor Azwin Hajri, Yosie Andriani, Aina Farahiyah Abdul Manan, Tengku Sifzizul Tengku Muhammad, Habsah Mohamad
Summary: Atherosclerosis, caused by elevated plasma cholesterols, is a major factor in global cardiovascular disease mortality. While statins are commonly used to lower cholesterol levels, they may have adverse effects, prompting the search for new treatments. Research on the marine invertebrate Acanthaster planci suggests its potential in reducing cholesterol levels without causing harm to the liver.
Article
Cardiac & Cardiovascular Systems
Michelle L. O'Donoghue, Robert P. Giugliano, Stephen D. Wiviott, Dan Atar, Anthony Keech, Julia F. Kuder, KyungAh Im, Sabina A. Murphy, Jose H. Flores-Arredondo, J. Antonio G. Lopez, Mary Elliott-Davey, Bei Wang, Maria Laura Monsalvo, Siddique Abbasi, Marc S. Sabatine
Summary: Long-term use of evolocumab to lower LDL-C levels is associated with low rates of adverse events, which do not exceed those in the placebo group. Over time, the use of evolocumab also leads to further reduction in cardiovascular events.
Article
Clinical Neurology
Zhirong Yang, Duncan Edwards, Stephen Burgess, Carol Brayne, Jonathan Mant
Summary: This study investigated the potential associations between blood LDL-C, HDL-C, and triglycerides and post-stroke dementia. The results showed that higher LDL-C levels were associated with an increased risk of dementia, while lower triglyceride levels were associated with a decreased risk. There was no association between HDL-C levels and dementia.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Environmental Sciences
Hannah Gardener, Qi Sun, Philippe Grandjean
Summary: This study found that pregnant U.S. women are widely exposed to PFAS in late pregnancy, with positive associations between PFAS exposure and serum-lipid concentrations. While most PFAS were not associated with birth weight, PFNA may be associated with preterm birth.
ENVIRONMENTAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Nurjannatul Naim Kamaruddin, Lukman Hakim Mohd Din, Allicia Jack, Aina Farahiyah Abdul Manan, Habsah Mohamad, Tengku Sifzizul Tengku Muhammad
Summary: This study investigated the effects of a selected fraction of A. planci on PCSK9 gene expression, LDLR protein level, and LDL-C uptake. The results showed that the selected fraction reduced PCSK9 gene expression, increased LDLR protein level, and promoted LDL-C uptake. These findings suggest that the selected fraction has the potential to lower circulating LDL-C levels and may be a promising therapeutic intervention for preventing the progression of atherosclerosis.
Article
Behavioral Sciences
Andrew S. Bell, Josephin Wagner, Daniel B. Rosoff, Falk W. Lohoff
Summary: The gene encoding PCSK9 and its protein product have been widely studied for their role in cholesterol and lipid metabolism. There is a growing body of evidence that PCSK9 plays a crucial role in pathogenic processes in other organ systems, including the central nervous system. PCSK9's impact on the brain is not yet fully understood, but recent studies have sought to illuminate its connection with neurodegenerative and psychiatric disorders. The review aims to describe PCSK9's role in the central nervous system, examine its potential in disease outcomes, and explore the clinical potential of PCSK9 inhibitors and genetic variation in the PCSK9 gene.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
Paul F. Lebeau, Jae Hyun Byun, Khrystyna Platko, Paul Saliba, Matthew Sguazzin, Melissa E. MacDonald, Guillaume Pare, Gregory R. Steinberg, Luke J. Janssen, Suleiman A. Igdoura, Mark A. Tarnopolsky, S. R. Wayne Chen, Nabil G. Seidah, Jakob Magolan, Richard C. Austin
Summary: Caffeine inhibits the activation of SREBP2 to promote LDLc clearance and reduce the risk of cardiovascular disease.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Justin R. Clark, Matthew Gemin, Amer Youssef, Santica M. Marcovina, Annik Prat, Nabil G. Seidah, Robert A. Hegele, Michael B. Boffa, Marlys L. Koschinsky
Summary: Elevated plasma lipoprotein(a) (Lp(a)) is an independent, causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Sortilin may play a role in determining plasma levels of Lp(a) and is associated with the secretion of apo(a) and apoB.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Virology
Rachid Essalmani, Jaspreet Jain, Delia Susan-Resiga, Ursula Andreo, Alexandra Evagelidis, Rabeb Mouna Derbali, David N. Huynh, Frederic Dallaire, Melanie Laporte, Adrien Delpal, Priscila Sutto-Ortiz, Bruno Coutard, Claudine Mapa, Keith Wilcoxen, Etienne Decroly, Tram Nq Pham, Eric A. Cohen, Nabil G. Seidah
Summary: The spike protein of SARS-CoV-2 plays a crucial role in infecting the lungs and other tissues by binding to the ACE2 receptor. Cleavage of the spike protein at S1/S2 and S2' sites is important for viral entry and fusion. This study identifies the fusion activation site S2' as KPSKR815 down arrow and demonstrates that its cleavage is enhanced by ACE2 engagement. The combination of furin and TMPRSS2 inhibitors shows promise as potent antivirals against SARS-CoV-2.
JOURNAL OF VIROLOGY
(2022)
Article
Medicine, General & Internal
Husain Y. Alkhaldy, Zuhier A. Awan, Ahmed A. Abouzaid, Hossameldin M. Elbahaey, Saeed M. Al Amoudi, Shehata F. Shehata, Muhammad Saboor
Summary: This study compared blood counts at different altitudes and sea level and suggested a correction factor for altitude-related increment in hemoglobin and red blood cell indices. The results showed that there were significant differences in hemoglobin and other red cell indices among men and women at different altitudes in Saudi Arabia. The study also proposed a correction factor for individuals living at high altitudes in Saudi Arabia.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2022)
Review
Peripheral Vascular Disease
Nabil G. Seidah, Damien Garcon
Summary: Since the discovery of PCSK9 in 2003, it has been found to play roles not only in regulating LDL-cholesterol, but also in inflammation, pathogen infections, and cellular proliferation in various cancers and associated metastases.
CURRENT ATHEROSCLEROSIS REPORTS
(2022)
Article
Engineering, Biomedical
Jessie R. Davis, Xiao Wang, Isaac P. Witte, Tony P. Huang, Jonathan M. Levy, Aditya Raguram, Samagya Banskota, Nabil G. Seidah, Kiran Musunuru, David R. Liu
Summary: Compact adenine base editors (ABEs) encoded within size-optimized genomes of adeno-associated viruses (AAVs) enable therapeutic base editing in mice at low doses and high editing efficiencies, simplifying AAV production and characterization.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Chemistry, Medicinal
Ahmed K. Kammoun, Maha A. Hegazy, Alaa Khedr, Zuhier Ahmed Awan, Maan T. Khayat, Majid Mohammad Al-Sawahli
Summary: This study aimed to enhance the purposing profile of Etodolac (ETD) in Human Hepatocellular Carcinoma (HCC) HepG2 cells using sodium deoxycholate stabilized zein nanospheres (ETD-SDZN NSs). The ETD-SDZN NSs showed improved cellular uptake, accumulation in G2-M phase, elevated mRNA expression of P53, reduced expression of CDK1 and COX-2, enhanced oxidative stress, and superior cell death-inducing profile compared to free ETD. The formulation method successfully obtained a promising therapeutic profile for ETD in HCC.
Article
Biology
Abdullah A. Alamoudi, Awaad S. Alharbi, Ashraf B. Abdel-Naim, Shaimaa M. Badr-Eldin, Zuhier A. Awan, Solomon Z. Okbazghi, Osama A. A. Ahmed, Nabil A. Alhakamy, Usama A. Fahmy, Ahmed Esmat
Summary: Diabetic hyperglycemia delays wound healing, but the ion-paired CTX-APA nanocomplex can promote wound healing in diabetic rats.
Review
Polymer Science
Renatha Jiffrin, Saiful Izwan Abd Razak, Mohamad Ikhwan Jamaludin, Amir Syahir Amir Hamzah, Muadz Ahmad Mazian, Muhammad Azan Tamar Jaya, Mohammed Z. Nasrullah, Mohammed Majrashi, Abdulrahman Theyab, Ahmed A. Aldarmahi, Zuhier Awan, Mohamed M. Abdel-Daim, Abul Kalam Azad
Summary: Electrospinning is a promising method for creating nanofiber membranes that can release drugs over time. These nanofiber composites have a large surface area to volume ratio, which aids in cell binding, drug loading, and mass transfer processes.
Article
Oncology
Yan Gu, Xiaozeng Lin, Ying Dong, Geoffrey Wood, Nabil G. Seidah, Geoff Werstuck, Pierre Major, Michael Bonert, Anil Kapoor, Damu Tang
Summary: This study found that tumor-derived PCSK9 is closely associated with the development of melanoma and promotes tumor growth by regulating cholesterol metabolism and influencing the immune system. The study also identified PCSK9 as a potential biomarker for predicting the efficacy of immune checkpoint blockade therapy.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Virology
Rachid Essalmani, Ursula Andreo, Alexandra Evagelidis, Mailys Le Devehat, Oscar Henrique Pereira Ramos, Carole Fruchart Gaillard, Delia Susan-Resiga, Eric A. Cohen, Nabil G. Seidah
Summary: This study investigates the involvement of cholesterol-regulating enzymes SKI-1 and PCSK9 in the entry of SARS-CoV-2. SKI-1 enhances cell-to-cell fusion by activating SREBP-2, while PCSK9 reduces cell-to-cell fusion by promoting the degradation of ACE2. Both SKI-1 and PCSK9 modulate SARS-CoV-2 entry through independent mechanisms.
Letter
Biochemistry & Molecular Biology
Anna Roubtsova, Corey A. Scipione, Damien Garcon, Michael B. Boffa, Nabil G. Seidah, Marlys L. Koschinsky, Annik Prat
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Biochemistry & Molecular Biology
Heba A. El-Dash, Nehal E. Yousef, Abeer A. Aboelazm, Zuhier A. Awan, Galal Yahya, Amira M. El-Ganiny
Summary: A large amount of plastics are introduced into the ecosystem worldwide, causing environmental pollution. This study aims to isolate plastic-biodegrading fungi and explore optimum conditions for their action. Results showed that 10 isolates were able to degrade polyvinyl chloride (PVC) polymer, and three isolates displayed superior PVC-biodegrading activity under specific temperature and pH conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Abdulhadi Bima, Basmah Eldakhakhny, Aliaa A. Alamoudi, Zuhier Awan, Abrar Alnami, Salwa Mohamed Abo-Elkhair, Hussein Sakr, Fatma Mohamed Ghoneim, Ayman Elsamanoudy
Summary: This study investigates the relationship between brain insulin resistance and metabolic syndrome (MetS) and examines the protective effects of a low-carbohydrate, high-fat (LCHF) diet. The results suggest that MetS is associated with dysregulated gene expression in the brain, while the LCHF diet shows a protective effect against these abnormalities.
Article
Health Care Sciences & Services
Mohammad A. Alfhili, Jawaher Alsughayyir, Ahmed M. Basudan, Roua Alsubki, Saleh Alqahtani, Zuhier A. Awan, Mohammed R. Algethami, Yazeed A. Al-Sheikh
Summary: This study found that elevated monocyte-lymphocyte ratio (MLR) is associated with an increased risk of impaired fasting glycemia (IFG) and hyperglycemia (HG). Large prospective cohort studies are needed to establish the temporal relationship between MLR and fasting blood glucose (FBG) and to examine the prognostic value of this novel marker.