Review
Chemistry, Multidisciplinary
Le-chun Ou, Shan Zhong, Jing-song Ou, Jin-wei Tian
Summary: Atherosclerosis is the main pathological cause of coronary heart disease, and current clinical interventions are relatively effective for early plaque but not ideal for advanced AS, resulting in high residual risk. Nanomedicine shows great potential in anti-AS therapy, with targeted nanoparticles becoming an important strategy to further reduce residual risk of cardiovascular events. Feasibility and safety of nanotechnology in clinical treatment have been preliminarily confirmed.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Nutrition & Dietetics
Eberhard Windler, Frank-Ulrich Beil, Heiner K. Berthold, Ioanna Gouni-Berthold, Ursula Kassner, Gerald Klose, Stefan Lorkowski, Winfried Maerz, Klaus G. Parhofer, Jogchum Plat, Guenter Silbernagel, Elisabeth Steinhagen-Thiessen, Oliver Weingaertner, Birgit-Christiane Zyriax, Dieter Luetjohann
Summary: Phytosterols (PSs) have been proposed as a dietary means to lower plasma LDL-C. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular events. PSs offer a dietary approach to cholesterol management based on their LDL-C lowering and absence of adverse safety signals.
Article
Multidisciplinary Sciences
Qianqian Bai, Yu Xiao, Huiling Hong, Xiaoyun Cao, Lei Zhang, Ruifang Han, Leo Kit Cheung Lee, Evelyn Y. Xue, Xiao Yu Tian, Chung Hang Jonathan Choi
Summary: This study demonstrates the use of a three-dimensional nanostructure for delivering therapeutic oligonucleotides to atherosclerotic plaques. The nanoparticles target specific cells in the plaques and modulate genes related to plaque formation and inflammation, resulting in reduced and stabilized plaques without severe toxicity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Crystallography
Mihai Stefan Cristian Haba, Dragomir N. Serban, Lacramioara Serban, Ivona Maria Tudorancea, Raluca Maria Haba, Ovidiu Mitu, Radu Iliescu, Ionut Tudorancea
Summary: Cardiovascular diseases (CVDs) are a significant epidemic affecting over 37 million patients worldwide. Current therapies focus on symptom relief, but the use of nanoparticles for diagnosis and treatment shows great potential in targeting CVDs.
Article
Biochemistry & Molecular Biology
Go Eun Kwon, Myung Han Hyun, Dong Jun Byun, Ki-Jung Paeng, Hong Seog Seo, Man Ho Choi
Summary: This study identified metabolic signatures of serum sterols related to cardiovascular disease severity, showing close associations between cholesterol levels and CVD risk factors. Interventions such as statin treatment were found to impact cholesterol metabolism, with potential implications for cardiovascular health.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Chongxu Shi, Elmina Mammadova-Bach, Cong Li, Dong Liu, Hans-Joachim Anders
Summary: Cholesterol crystal (CC) embolism is a complication of advanced atherosclerotic plaques primarily induced by interventional and surgical procedures. Prophylaxis through plaque stabilization and avoiding unnecessary catheter interventions is the main approach to CC embolism. Platelet inhibitors and anticoagulants may reduce the risk of vascular occlusions and tissue ischemia in case CC embolism occurs. Given the unmet medical need, effective treatment strategies for CC embolism are urgently needed.
Article
Chemistry, Multidisciplinary
Zhengyu Cao, Guotao Yuan, Lingli Zeng, Lu Bai, Xiao Liu, Maoxiong Wu, Runlu Sun, Zhiteng Chen, Yuan Jiang, Qingyuan Gao, Yangxin Chen, Yuling Zhang, Yue Pan, Jingfeng Wang
Summary: Sonodynamic therapy (SDT) and photothermal therapy (PTT) are combined using hyaluronic acid and PEG-modified copper sulfide/titanium oxide heterostructure nanosheets to target and treat early atherosclerotic plaques. The synergistic therapy induces apoptosis of proinflammatory macrophages, reduces heat shock protein 90 expression, and mitigates inflammation, preventing plaque progression.
Review
Biochemistry & Molecular Biology
Enrica Rossini, Federico Biscetti, Maria Margherita Rando, Elisabetta Nardella, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Marcello Covino, Antonio Gasbarrini, Massimo Massetti, Andrea Flex
Summary: Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality in high-income countries, although its impact is decreasing. Statins are effective in reducing LDL cholesterol and the risk of mortality, but are under-prescribed or under-dosed due to concerns about side effects. Personalized treatment decisions should be made based on individual considerations and shared decision-making.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Toxicology
Charles A. German, James K. Liao
Summary: Statins not only reduce LDL-C through inhibition of the key rate-limiting step in the cholesterol biosynthetic pathway, but also improve serum clearance by upregulating the expression of LDL receptors. They may exert various pleiotropic effects, such as improving plaque stability, reducing inflammation and thrombosis, decreasing oxidative stress, and improving endothelial function and vascular tone. However, they also have potential harmful pleiotropic effects, including increased risk of muscle-related side effects, diabetes, hemorrhagic stroke, and cognitive decline.
ARCHIVES OF TOXICOLOGY
(2023)
Editorial Material
Public, Environmental & Occupational Health
Robert DuBroff, Maryanne Demasi
Summary: Recent studies suggest that lowering cholesterol may not be the best way to prevent coronary heart disease, and other factors such as insulin resistance or remnant cholesterol may be more important. The effectiveness of therapies designed to prevent heart disease by lowering cholesterol with drugs or diet has been inconsistent.
PREVENTIVE MEDICINE
(2021)
Review
Endocrinology & Metabolism
David S. Schade, Kristen Gonzales, Neil Kaminsky, Allen Adolphe, Lynda Shey, Robert Philip Eaton
Summary: Cardiovascular disease is the leading cause of death. Many patients struggle to achieve the American Heart Association's LDL cholesterol treatment goals. The importance of a low cholesterol diet is controversial and often overlooked by physicians. Determining an individual's ability to absorb dietary cholesterol and their baseline cholesterol and saturated fat intake is critical in assessing the impact of egg yolk cholesterol and saturated fat on blood LDL cholesterol. Currently, there are no available blood tests to directly measure this effect, but a one-month trial of a low cholesterol and saturated fat diet can provide valuable information for clinical decision-making.
ENDOCRINE PRACTICE
(2022)
Review
Medicine, General & Internal
Pier Luigi Temporelli, Marcello Arca, Laura D'Erasmo, Raffaele De Caterina
Summary: Hyperlipidemia is a significant risk factor for coronary heart disease, but its relationship to stroke has been less clear. Recent data demonstrate the positive impact of cholesterol-lowering on stroke, while also dispelling concerns about increased risk of hemorrhagic stroke. Despite guidelines recommending aggressive lipid-lowering therapy for at-risk patients, secondary prevention patients often do not receive adequate treatment.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Charlie Harper, Marion Mafham, William Herrington, Natalie Staplin, William Stevens, Karl Wallendszus, Richard Haynes, Martin J. Landray, Sarah Parish, Louise Bowman, Jane Armitage
Summary: Post hoc analyses of the ASCEND trial suggest that routinely collected hospital admission and death registry data in the UK could be used as the sole method of follow-up for myocardial infarction, ischemic stroke resulting in hospitalization, vascular death, and arterial revascularization in primary prevention cardiovascular trials, without the need for verification by clinical adjudication.
Article
Biochemistry & Molecular Biology
Laeticia Scherler, Sofia N. Verouti, Daniel Ackermann, Bruno Vogt, Genevieve Escher
Summary: In this study, adenine was used to induce nephropathy in mice, showing the loss of protective effects of renal cholesterol and vitamin D-3 metabolism under this condition. It was found that adenine enhanced cholesterol efflux and eliminated lipids in feces, which had a protective effect against atherosclerosis but also affected bone growth.
Article
Biotechnology & Applied Microbiology
Joon Woo Song, Jae Won Ahn, Min Woo Lee, Hyun Jung Kim, Dong Oh Kang, Ryeong Hyun Kim, Un Gyo Kang, Yeon Hoon Kim, Jeongmoo Han, Ye Hee Park, Hyeong Soo Nam, Hongki Yoo, Kyeongsoon Park, Jin Won Kim
Summary: A macrophage targetable near-infrared fluorescence emitting phototheranostic agent was developed to reduce both plaque burden and inflammation in murine atheroma through the harmonic contribution of apoptosis, autophagy, and lesional efferocytosis. This strategy shows promising potential as a theranostic approach for high-risk atheroma.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Joseph Ali, Jong Bong Lee, Sally Gittings, Alessandro Iachelini, Joanne Bennett, Anne Cram, Martin Garnett, Clive J. Roberts, Pavel Gershkovich
Summary: This study developed biorelevant simulated salivary fluids for uniform application in oral cavity dissolution testing. Comparative physicochemical properties and dissolution profiles demonstrated the bioequivalence of the developed simulated saliva, providing a basis for standardized dissolution tests in future oral cavity studies.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Wanshan Feng, Chaolong Qin, YenJu Chu, Mattia Berton, Jong Bong Lee, Atheer Zgair, Sara Bettonte, Michael J. Stocks, Cris S. Constantinescu, David A. Barrett, Peter M. Fischer, Pavel Gershkovich
Summary: Lipid-based formulations are important for delivering lipophilic drugs orally. A study on the use of pre-digested lipid formulations to improve intestinal lymphatic transport and oral bioavailability of CBD showed that natural sesame oil was more effective than pre-digested or purified forms. Further research is needed to explore the mechanisms involved in sesame oil's superior performance in oral absorption.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Nanoscience & Nanotechnology
Vahid Heravi Shargh, Jeni Luckett, Kaouthar Bouzinab, Stephen Paisey, Lyudmila Turyanska, William G. B. Singleton, Stephen Lowis, Pavel Gershkovich, Tracey D. Bradshaw, Malcolm F. G. Stevens, Alison Bienemann, Beth Coyle
Summary: The study introduces N3P nanoparticles as a promising approach for treating TMZ-resistant DIPG, showing strong anticancer efficacy and overcoming drug resistance. Additionally, dynamic PET scans demonstrate localized distribution and retention of the nanoparticles in the rat brain following administration through CED.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Pharmacology & Pharmacy
Jong Bong Lee, Xiaowei Zang, Atheer Zgair, Ting Qian Ooi, David W. Foley, Gregory Voronin, Leonid Kagan, Fadi Soukarieh, Rui Gao, Hao Shao, Wan Tying Soh, Tae Hwan Kim, Min Gi Kim, Hwi-yeol Yun, Anthony J. Wilson, Peter M. Fischer, Pavel Gershkovich
Summary: Oral administration route is preferred for treating chronic cancers, but the advantages of oral chemotherapy can be limited by unfavorable pharmacokinetics. This study successfully improved the oral bioavailability of a promising drug candidate for CDK9 inhibitor by assessing and optimizing its biopharmaceutical properties.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Yenju Chu, Chaolong Qin, Wanshan Feng, Charles Sheriston, Yu Jane Khor, Concepcion Medrano-Padial, Birgit E. Watson, Teddy Chan, Binhua Ling, Michael J. Stocks, Peter M. Fischer, Pavel Gershkovich
Summary: The study indicates that the use of LCT-based formulation approach alone is not sufficient for effective delivery of TPV to MLNs. Future efforts should be directed towards a combined highly lipophilic prodrugs/lipid-based formulation approach to target TPV, other PIs, and potentially other classes of antiretroviral agents to viral reservoirs within the mesenteric lymphatic system.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Wanshan Feng, Chaolong Qin, Elena Cipolla, Jong Bong Lee, Atheer Zgair, Yenju Chu, Catherine A. Ortori, Michael J. Stocks, Cris S. Constantinescu, David A. Barrett, Peter M. Fischer, Pavel Gershkovich
Summary: Oral sesame oil-based formulation helps deliver CBD to the lymphatic system and blood circulation, but also leads to variability in absorption. Adding MCT to the formulation increases CBD distribution into the micellar phase, while surfactants do not further enhance this distribution. MCT improves emulsification and micellar solubilization of CBD, reducing variability in concentrations in vivo.
Article
Pharmacology & Pharmacy
Sarah Sulaiman, Pavel Gershkovich, Caroline L. Hoad, Matthew Calladine, Robin C. Spiller, Snow Stolnik, Luca Marciani
Summary: Oral specially coated formulations have the potential to improve treatment outcomes of diseases in the distal intestinal tract. A feasibility study using MRI imaging showed that tracking and assessing integrity of coated capsules in the gastrointestinal tract is possible.
Article
Pharmacology & Pharmacy
Adelaide Jewell, Alice Brookes, Wanshan Feng, Marianne Ashford, Paul Gellert, James Butler, Peter M. Fischer, David J. Scurr, Michael J. Stocks, Pavel Gershkovich
Summary: This study assessed the distribution of highly lipophilic drug cannabidiol (CBD) in specific mesenteric lymph nodes (MLN) and retroperitoneal lymph nodes (RPLN) following oral administration with lipids. The results showed that CBD concentrations were significantly higher in the region second from the apex of the MLN chain at 2 hours post dosing. From 3 hours post dosing, concentrations in all MLN were similar. CBD was also found at substantial levels in RPLN.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Alice Brookes, Liuhang Ji, Tracey D. Bradshaw, Michael Stocks, David Gray, James Butler, Pavel Gershkovich
Summary: This review explores the feasibility of oral lipid-based drug delivery to the brain and discusses various lipids that can potentially be delivered orally. Current data suggests that oral administration can increase the permeability of the blood-brain barrier (BBB), and further research is needed to investigate the use of lipid-based drug delivery for brain targeting.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Christina Priest, Rohith T. Nagari, Lara Bideyan, Stephen D. Lee, Alexander Nguyen, Xu Xiao, Peter Tontonoz
Summary: The study illustrates the role of BRAP in modulating the hepatic Hippo pathway by regulating MST2, impacting liver cell morphology and turnover. Loss of BRAP leads to significant morphological changes in the liver, increased hepatocyte proliferation, cell death, and inflammation. The altered Hippo pathway signaling in Brap knockout mice affects liver lipid accumulation in dietary models of obesity, highlighting its relevance to human liver disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Wanshan Feng, Chaolong Qin, Salah Abdelrazig, Ziyu Bai, Mekha Raji, Randa Darwish, YenJu Chu, Liuhang Ji, David A. Gray, Michael J. Stocks, Cris S. Constantinescu, David A. Barrett, Peter M. Fischer, Pavel Gershkovich
Summary: This study investigated the composition differences of different vegetable oils and their effects on promoting CBD lymphatic targeting and bioavailability. The results showed that olive oil led to the highest concentration of CBD in the lymphatic system and in the systemic circulation following oral administration.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Editorial Material
Pharmacology & Pharmacy
Sifei Han, Natalie Trevaskis, Pavel Gershkovich, Leonid Kagan
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Paula Muresan, Phoebe McCrorie, Fiona Smith, Catherine Vasey, Vincenzo Taresco, David J. Scurr, Stefanie Kern, Stuart Smith, Pavel Gershkovich, Ruman Rahman, Maria Marlow
Summary: This study developed polymeric microneedle (MN) patches for the treatment of CNS tumors. The results demonstrated successful drug release and penetration, providing a potential solution for local brain drug delivery.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Alice Brookes, Adelaide Jewell, Wanshan Feng, Tracey D. Bradshaw, James Butler, Pavel Gershkovich
Summary: This study investigated the delivery of cannabidiol (CBD) to the brain following oral administration in lipid-based and lipid-free vehicles. It was observed that different formulations resulted in different CBD delivery to the whole brain and various brain regions, indicating the importance of oral formulation selection for optimal delivery to specific brain regions.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Yenju Chu, Abigail Wong, Haojie Chen, Liuhang Ji, Chaolong Qin, Wanshan Feng, Michael J. Stocks, Pavel Gershkovich
Summary: A military helicopter crash in Vietnam resulted in 13 deaths and 3 injuries. The cause of the accident is under investigation.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)