Effect of garlic on cardiovascular disorders: a review

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic

Extreme disorder in an ultrahigh-affinity protein complex

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

Ekaterina A Ivanova,1 Yuri V Bobryshev,2,3 Alexander N Orekhov2,4,5 1Department of Pediatric Nephrology and Growth and Regeneration, Katholieke Universiteit Leuven and University Hospitals Leuven, Leuven, Belgium; 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia; 3Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, Sydney, NSW, Australia; 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia; 5Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia Abstract: High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(−)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(−), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk. Keywords: low-density lipoprotein, LDL, LDL electronegativity index, cardiovascular disease, atherosclerosi

Mitochondrial genome variability: the effect on cellular functional activity

Aleksandrina S Volobueva,1 Alexandra A Melnichenko,2 Andrey V Grechko,3 Alexander N Orekhov2,4 1Laboratory of Gene Therapy, Biocad Biotechnology Company, Saint-Petersburg, Strelnya, Russia; 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia; 3Federal Scientific Clinical Center for Resuscitation and Rehabilitation, Moscow, Russia; 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia Abstract: Mitochondria are the key players in cell metabolism, calcium homeostasis, and reactive oxygen species (ROS) production. Mitochondrial genome alterations are reported to be associated with numerous human disorders affecting nearly all tissues. In this review, we discuss the available information on the involvement of mitochondrial DNA (mtDNA) mutations in cell dysfunction. Keywords: mitochondria, mutation, apoptosis, reactive oxygen species, ATP, electron transfer chai

Inhibition of sialidase activity as a therapeutic approach

Victor Yu Glanz,1 Veronika A Myasoedova,2 Andrey V Grechko,3 Alexander N Orekhov2,4 1Department of Genetics, Cytology and Bioengineering, Faculty of Biology and Medicine, Voronezh State University, Voronezh, Russia; 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russia; 3Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia; 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia Abstract: The demand for novel anti-influenza drugs persists, which is highlighted by the recent pandemics of influenza affecting thousands of people across the globe. One of the approaches to block the virus spreading is inhibiting viral sialidase (neuraminidase). This enzyme cleaves the sialic acid link between the newly formed virions and the host cell surface liberating the virions from the cell and maintaining the cycle of infection. Viral neuraminidases appear therefore as attractive therapeutic targets for preventing further spread of influenza infection. Compared to ion channel blockers that were the first approved anti-influenza drugs, neuraminidase inhibitors are well tolerated and target both influenza A and B viruses. Moreover, neuraminidase/sialidase inhibitors may be useful for managing some other human pathologies, such as cancer. In this review, we discuss the available knowledge on neuraminidase or sialidase inhibitors, their design, clinical application, and the current challenges. Keywords: sialidase, neuraminidase, neuraminidase inhibitor, influenza, drug desig