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Strategies, Design, and Chemistry in Small Interfering RNA Delivery Vehicle Systems for Cancer Therapy
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
The synthesis of siRNA is based on the research that originated in 1950s [209]. In 1978, Zamecnik and Stephenson reported that a synthetic oligonucleotide complementary to Rous sarcoma virus 35S RNA could inhibit protein expression [210,211]. This work reported that a synthetic antisense oligonucleotide (ASO) could bind to a target mRNA through Watson-Crick base pairing led to substantial research development of ASOs as therapeutics. In 2013, the FDA approved mipomersen, an ASO against apolipoprotein B, for the treatment of homozygous familial hypercholesterolemia [212]. Nusinersen (Spinraza) was later approved by the FDA in 2016 for the indication of spinal muscular atrophy [213]. In general, ASOs do not function in vivo through the RNAi pathway and therefore are not considered siRNAs [214]. Nonetheless, research on ASOs provided the basis for much of the chemistry used in siRNA synthesis and chemical modification today.
The Promise of Artificial Intelligence and Machine Learning
Published in Paul Cerrato, John Halamka, Reinventing Clinical Decision Support, 2020
Machine learning is infusing new hope into the quest to improve detection rates in familial hypercholesterolemia (FH). FH, a significant cause of premature heart disease and death, affects approximately one in 250 individuals, yet the current detection rate is abysmal: Less than 10% of persons with the disorder in the United States are identified.33 Juan Banda, with the Center for Biomedical Informatics Research, Stanford University, and his colleagues at other universities have developed a deep learning classifier that is much more likely to find these patients. Considering the fact that a person with this monogenic disorder is twenty times more likely to develop atherosclerotic cardiovascular disease than someone with normal LDL levels, it is hard to imagine the algorithm not benefiting patients with this disorder—or their at-risk relatives.
Steroids: Arthritis, Fertility, Heart Attacks, And Home Run Records
Published in Richard J. Sundberg, The Chemical Century, 2017
The association between cholesterol levels and cardiovascular disease began to be recognized around 1900, when it was observed that animals fed high cholesterol diets developed atherosclerosis. A genetic disorder, familial hypercholesterolemia, is characterized by both very high cholesterol levels and early onset of cardiovascular disease. The Framingham Heart Study of the National Institutes of Health provided convincing statistical evidence of a correlation between blood cholesterol levels and the incidence of heart disease.6 It was also recognized that a high ratio of low-density lipoprotein (LDL) to high-density lipoprotein (HDL) was a risk factor for cardiovascular disease.7 These values, in turn, are influenced by dietary intake, with saturated fat and trans-fat tending to increase LDL while unsaturated fats decrease LDL. Cardiovascular disease is a major cause of death in most of the developed world and accounts for about 15% of deaths in the United States, of which about 15% are <65 years of age. There are associations of cardiovascular diseases with several factors, including those that constitute the metabolic syndrome, namely obesity, hypertension, and insulin resistance.
Cholesterol removal from human plasma with biologically modified cryogels
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Gizem Uzunoğlu, Duygu Çimen, Nilay Bereli, Kemal Çetin, Adil Denizli
Cardiovascular disease (CVD) is a class of diseases involving both the heart and blood vessels, therefore, including myocardial infarction, angina, stroke, hypertensive heart disease, cardiomyopathy, congenital heart disease, aortic aneurysms, carditis and so on [1–3]. Studies show that there is a correlation between serum cholesterol levels and cardiovascular diseases [4–6]. According to clinical and epidemiological investigations, the risk of CVD is directly related with low-density lipoprotein-cholesterol (LDL-C) while it is inversely associated with high-density lipoprotein-cholesterol (HDL-C) [7–9]. One of the CVDs caused by high levels of LDL-C and triglycerides is atherosclerosis, a chronic inflammatory process including the vascular walls [10]. Lipid-lowering drugs are used to reduce elevated blood levels of LDL-C in patients with atherosclerosis [11]. However, the efficiency of these drugs is limited and they might cause liver injury [12]. In addition, familial hypercholesterolemia is not sufficiently treated with lipid-lowering drugs [12]. Therefore, new biotechnological and biomedical improvements have been gaining importance in removal of LDL-C from blood plasma.
Effects of footwear and heel elevation on tensile load in the Achilles tendon during treadmill walking†
Published in Footwear Science, 2018
Torsten Brauner, Sue Hooper, Thomas Horstmann, Scott Wearing
Twenty healthy adults (age: 31 ± 9 years; height: 1.72 ± 0.04 m; weight: 67.8 ± 14.2 kg), recruited from university students and faculty, participated in the study. Male (n = 10) and female (n = 10) participants reported the conventional use of size 9 and 10 running shoes during physical activity, respectively. A Brannock® foot-measuring device (The Brannock Device Co., New York, USA) was used to confirm the shoe size of each participant. No participant reported a medical history of diabetes, familial hypercholesterolemia, inflammatory arthritis, or Achilles tendon injury or pathology. Participant numbers were based on previously published data for human Achilles tendon (Wulf et al., 2016), and were sufficient to detect a 3% difference in the peak axial velocity of ultrasound (α = .05, β = .20). The study received approval from the University Human Research Ethics Committee and all participants gave written informed consent prior to their participation.
Reproductive outcomes in rat female offspring from male rats co-exposed to rosuvastatin and ascorbic acid during pre-puberty
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Gabriel Adan Araujo Leite, Thamiris Moreira Figueiredo, Tainá Louise Pacheco, Marina Trevizan Guerra, Janete Aparecida Anselmo-Franci, Wilma De Grava Kempinas
Previous studies reported that pediatric dyslipidemias may be linked to genetic factors such as familial hypercholesterolemia (Cook and Kavey 2011; Ross 2016) or associated with environmental factors such as inappropriate lifestyle, lack of physical exercises and bad eating habits (Izar, Fonseca, and Fonseca 2011; Ross 2016). American Academy of Pediatrics and The National Heart, Lung and Blood Institute recommended lipid-lowering drugs to treat dyslipidemias in children aged 8 to 10 years when diet and physical exercises were not sufficient to lower LDL-cholesterol (Joyce et al. 2016). However, Araujo and Pacce (2016) proposed to treat dyslipidemias in children with statins from 8 to 12 years.