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Current Pharmaceutical Design

Mikhail Konoplyannikov, Svetlana Kotova, Vladimir Baklaushev, Anatoly Konoplyannikov, Vladimir Kalsin, Peter Timashev, Alexander Troitsky
Ischemic heart disease (IHD) has been recognized as the main cause of mortality in the modern world. Application of cell therapy technologies for the IHD treatment has been actively studied from the beginning of 2000s. The review is dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The strategies of the MSC modification in vitro for improvement of their regenerative potential are extensively discussed, including preconditioning to enhance the cell survival, boosting their paracrine effect, manipulating their cardiomyogenic differentiation...
September 13, 2018: Current Pharmaceutical Design
Pauline S Santos, Thaisa C Oliveira, Luis Mário R Júnior, Lívio C C Nunes
BACKGROUND: The β-caryophyllene (BCP), a phytocannabinoid presents in various essential oils, demonstrated selective action on the CB2 endocannabinoid receptor and attracted considerable attention because of its several pharmacological activities. Despite this recognized potential, this hydrophobic compound is a volatile and acid-sensitive sesquiterpene that readily oxidizes when exposed to air, and has low bioavailability in oral formulations. Thus, the development of formulations that guarantee its stability and increase its bioavailability is a challenge for its use in the pharmaceutical field...
September 12, 2018: Current Pharmaceutical Design
Luyao Li, Shiyao Xu, Tingtig Guo, Shouliang Gong, Chuan Zhang
OBJECTIVE: To investigate the effect of dapagliflozin on intestinal microflora in MafA-deficient mice by establishing an animal model of diabetes. METHODS: Male MafA knockout mice were given intragastrically with dapagliflozin (1.0 mg/kg/d) for 6 weeks. Body weights and fasting blood glucose levels were measured in mice, and their intestinal short-chain fatty acids were measured by gas chromatography. At the same time, a plate count method was used to analyze the number of main harmful bacteria in the feces and the high-throughput sequencing was used to sequence the changes of intestinal flora...
September 12, 2018: Current Pharmaceutical Design
R Varaeva Yurgita, N Elena Livantsova, V Igor Ukrainets, D Svetlana Kosyura, V Antonina Starodubova
The issue of vitamin deficiency persists to be a major health issue worldwide despite the advancements in medicine. At the same time, the effect of marginal vitamin deficiency status on physiological processes is proven. However, general methods such as immune-enzyme and fluorescence analysis, microbiological assays, for example, have limitations in vitamin status assessment and are not able to reliably reflect personal vitamin demand. The potential usefulness of modern metabolomics methods in vitamin status assessment is described in this review...
September 12, 2018: Current Pharmaceutical Design
Anna Aiello, Giuseppina Candore, Giulia Accardi, Calogero Caruso, Claudia Colomba, Giovanni Duro, Caterina Maria Gambino, Mattia Emanuela Ligotti, Danilo Di Bona
Killer immunoglobulin-like receptors regulate the activation of natural killer cells through their interaction with human leucocyte antigens. Killer immunoglobulin-like receptors and human leucocyte antigens loci are highly polymorphic, and some their combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating killer immunoglobulin-like receptors profiles may be detrimental in autoimmune pathogenesis, and specific killer immunoglobulin-like receptors genes may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen...
September 11, 2018: Current Pharmaceutical Design
Evangelos Oikonomou, Konstantinos Mourouzis, Georgia Vogiatzi, Gerasimos Siasos, Spyridon Deftereos, Spyridon Papaioannou, George Latsios, Sotiris Tsalamandris, Dimitris Tousoulis
The no-reflow phenomenon refers to the post-percutaneous coronary intervention condition in which, despite re-establishing epicardial coronary vessel patency, the flow to the previously ischemic myocardium is markedly reduced. When it does occur, it attenuates the beneficial effect of reperfusion therapy and substantial regions of the myocardium fail to receive adequate perfusion. The pathophysiology of this phenomenon is not completely understood. The possible mechanisms could be related to alterations in the microvascular circulation...
September 11, 2018: Current Pharmaceutical Design
Alexander N Orekhov, Yumiko Oishi, Nikita G Nikiforov, Andrey V Zhelankin, Larisa Dubrovsky, Igor A Sobenin, Alexander Kel, Daria Stelmashenko, Vsevolod J Makeev, Kathy Foxx, Xueting Jin, Howard S Kruth, Michael Bukrinsky
A hallmark of atherosclerosis is its complex pathogenesis, which is dependent on altered cholesterol metabolism and inflammation. Both arms of pathogenesis involve myeloid cells. Monocytes migrating into the arterial walls interact with modified low-density lipoprotein (LDL) particles, accumulate cholesterol and convert into foam cells, which promote plaque formation and also contribute to inflammation by producing pro-inflammatory cytokines. A number of studies characterized transcriptomics of macrophages following interaction with modified LDL, and revealed alteration of the expression of genes responsible for inflammatory response and cholesterol metabolism...
September 11, 2018: Current Pharmaceutical Design
Alexander N Orekhov, Nikita G Nikiforov, Natalia V Elizova, Gleb A Korobov, Anastasia V Aladinskaya, Igor A Sobenin, Yuri V Bobryshev
Disorders of the innate immune system and associated cytokine disturbances play an important role in atherosclerosis. Although both pro- and anti-inflammatory cytokines have been detected in human atherosclerotic lesions, quantitative data on their expression in early atherosclerotic lesions remains to be reported. We studied localization of a pro-inflammatory cytokine, tumor necrosis factor-α (TNFα), and anti-inflammatory chemokine, C-C motif chemokine ligand 18 (CCL18), in human aorta. The intensity of staining for TNFα and CCL18 in atherosclerotic lesions was higher than in uninvolved tissues...
September 11, 2018: Current Pharmaceutical Design
Sajedeh Gholipour, Robert D E Sewell, Zahra Lorigooini, Mahmoud Rafieian-Kopaei
Atherosclerosis is an inflammatory vascular disease that is characterized by progressive accumulation of cholesterol in the arterial walls and it is a major cause of cardiovascular disease. Issues related to the side effects of synthetic drugs have in recent times, led to the misuse of drugs, a lack of patient consultations, and consequently, a disruption in meticulous disease control. Therefore, a new insight into medicinal plants has recently emerged and much research has been conducted on these herbs in an attempt to prepare novel naturally based drugs...
September 11, 2018: Current Pharmaceutical Design
Yu-Li Shen, Xiao-Qin Li, Rong-Rong Pan, Wei Yue, Li-Jun Zhang, Hong Zhang
Hair loss may not be recognized as a life-threatening disorder. However, it has a great harm on a person's self-respect, mental health, and entirety quality of life. Androgenic alopecia (AGA) is the most common type of hair loss, which affects a great number of both men and women. Alopecia can be treated with various hair loss strategies, including hair transplant, cosmetics and medication. Medical treatment shows the outstanding ability in improving hair growth. Plenty of drugs prevent alopecia by inhibiting the secretion of male hormone...
September 10, 2018: Current Pharmaceutical Design
Kaneez Fatima, Shilu Mathew, Muhammed Faheem, Tahir Mehmood, Hadi Mohamad Yassine, Asmaa A Al Thani, Hany Abdel-Hafiz, Khalid Al Ghamdy, Ishtiaq Qadri
The FOXO (Forkhead box O) transcription factors are implicated in several signaling pathways and play a vital role in various cellular and physiological processes include, for instance, ROS (reactive oxygen species) response, cell proliferation, regulation of programmed cell death, longevity, metabolism and cancer and regulation of cell cycle. In humans, four FOXO members resemble similar structure and are known for their role in both regulation and functions. FOXO1 gene is highly expressed in adipose tissues and it affects the regulation of glycogenolysis and gluconeogenesis through insulin signaling...
September 10, 2018: Current Pharmaceutical Design
V P Karagodin, V N Sukhorukov, V A Myasoedova, A V Grechko, A N Orekhov
Sialic acid residues that make part of the cell surface repertoire of carbohydrate residues are implicated in various physiological processes and human pathologies. Sialidases, or neuraminidases, are the enzymes that are able to cleave and release the sialic acid residues, while trans-sialidases can transfer the residues from donor to acceptor molecules. They are important for processing the surface glycolipids and glycoproteins. Therapeutic potential of pharmacological sialidases inhibition is currently actively studied...
September 10, 2018: Current Pharmaceutical Design
Xiaomeng Ren, Xiaofeng Wang, Mengchen Yuan, Chao Tian, Huilong Li, Xinyu Yang, Xinye Li, Yanda Li, Yihan Yang, Nian Liu, Hongcai Shang, Yonghong Gao, Yanwei Xing
Atrial fibrillation (AF) is a frequent cardiac arrhythmia. It is a common major cause of serious diseases and is an increasing health-care burden. AF is associated with an excess amount of reactive oxygen species. In this review, we summarize several possible reactive oxygen species pathways that induce AF based on atrial electrical and structural remodeling data. The sources and factors implicated in AF-related oxidative stress include NADPH oxidase activation, calcium overloading and mitochondrial damage, angiotensin system activation, nitric oxide synthase uncoupling, and xanthine oxidase activation-associated cardiovascular conditions...
September 3, 2018: Current Pharmaceutical Design
Arquimedes Gasparotto, Francislaine Aparecida Dos Reis
Hypertension is a non-transmissible chronic disease with a high prevalence, morbidity, and mortality. Different strategies for the treatment of hypertension are employed worldwide, but the control of hypertension remains a major challenge for global health. Many unsuccessful unconventional therapies have been proposed in recent years, including herbal medicines and the development of small molecules or antibodies that seek to disrupt the disease's pathogenesis. Cell-based therapies may be used as replacement or complementary treatment strategies...
September 3, 2018: Current Pharmaceutical Design
Sowndramalingam Sankaralingam, Angham Ahmed, Mizanur Rahman, Ali H Eid, Shankar Munusamy
BACKGROUND: The incidence and prevalence of diabetes mellitus are increasing globally at alarming rates. Cardiovascular and renal complications are the major cause of morbidity and mortality in patients with diabetes. Methylglyoxal (MG) - a highly reactive dicarbonyl compound - is increased in patients with diabetes and has been implicated to play a detrimental role in the etiology of cardiovascular and renal complications. Derived from glucose, MG binds to arginine and lysine residues in proteins, and the resultant end products serve as surrogate markers of MG generation in vivo...
September 3, 2018: Current Pharmaceutical Design
Xinye Li, Xinyu Yang, Yanda Li, Mengchen Yuan, Chao Tian, Yihan Yang, Xiaoyu Zhang, Chao Liu, Yonghong Gao, Nian Liu, Hongcai Shang, Yanwei Xing
Atrial fibrillation (AF) is the most common and significant cardiac arrhythmia in clinical practice, however the pathophysiological mechanism of AF has not been fully explained. At present, there are no available treatment options can target the underlying pathophysiological processes of AF. Research on improving management strategies for AF can start with a further understanding of the changes of cells in AF. Mitochondria play central roles in the function of cardiac myocytes and many of the pathophysiological processes implicated in AF are relative to mitochondrial function, including formation of reactive oxygen species (ROS), calcium homeostasis, and alterations of oxygen consumption...
September 3, 2018: Current Pharmaceutical Design
Selcuk Ozturk, Y Murat Elcin
For nearly a century, the adult heart was considered as a post-mitotic organ. The discovery of a resident cardiac stem cell (CSC) population in the heart has dramatically undermined this notion with the support of encouraging preclinical and clinical studies aiming to regenerate the damaged heart after a myocardial infarction (MI). There are two ways to obtain CSCs for transplantation: Allogeneic and autologous sources. Autologous cells may be obtained from the patients' own tissue. Obtaining cells from diseased patients may contain a risk for altered stem cell characteristics...
September 3, 2018: Current Pharmaceutical Design
Jamshid Tabeshpour, Amirhossein Sahebkar, Mohammad Reza Zirak, Majid Zeinali, Mahmoud Hashemzaei, Sajed Rakhshani, Saleh Rakhshani
Prediction of pharmacokinetics and drug targeting is a challenge in drug design. There are different types of software that can help predicting the pharmacokinetic profile of a drug. Quantitative structure-activity relationship (QSAR) modeling is used for drug design with less cost. Drug-excipient interactions are predicted by docking tools. Computerized drug target prediction and docking programs offer additional options to predict potential effects and adverse reactions of a given candidate as well as the best orientation of the compound on the receptor active site...
September 3, 2018: Current Pharmaceutical Design
Rui Lin, Shanshan Wang, Wentian Liu
A group of stimulus-responsive biopolymers developed from the hydrophobic domain of tropoelastin are collectively known as elastin-like polypeptides (ELPs). These peptides generally consist of repeated pentapeptide units of the form (VPGXG)n, where X can be any amino acid with the exception of proline. ELPs present wide-ranging possibilities in biomedicine due to their many beneficial characteristics, including tunable phase transition behavior and biological compatibility, along with the absence of immunogenic and pyrogenic characteristics...
September 3, 2018: Current Pharmaceutical Design
Kailash Prasad
Cardiovascular diseases (CVD) may be mediated through increases in the cardiovascular risk factors. Hemoglobin A1c (HbA1c) also called glycated hemoglobin is presently used for the diagnosis and management of diabetes. It has adverse effects on cardiovascular system. This review deals with its synthesis and effects on the cardiovascular system. The serum levels of HbA1c have been reported to be affected by various factors including, lifespan of erythrocytes, factors affecting erythropoiesis, agents interfering glycation of Hb, destruction of erythrocytes, drugs that shifts the formation of Hb, statins, and drugs interfering the HbA1c assay...
September 3, 2018: Current Pharmaceutical Design
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