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Gurpreet S Wander, Mohammed Yunus Khan Hukkeri, Sachin Yalagudri, Bharti Mahajan, Archana Toppo Panda
Cardiovascular (CV) diseases are a major cause of premature death and disability. Non-communicable diseases (NCD) are responsible for 52% of mortality amongst Indians, of these CV diseases are responsible for 66% of NCD mortality in India. We not only need widespread primary preventive strategy but also need effective secondary prevention protocols to reduce this. Secondary prevention in patients who already had myocardial infarction (MI) or revascularization is of utmost importance to reduce mortality, cardiac events and improve quality of life...
March 2018: Journal of the Association of Physicians of India
Brittany Z Suggs, Aislinn L Latham, Adriana T Dawes, Helen M Chamberlin
FACT (facilitates chromatin transcription) is a histone chaperone complex important in genomic processes including transcription, DNA replication, and DNA repair. FACT is composed of two proteins, SSRP1 and SPT16, which are highly conserved across eukaryotes. While the mechanisms for FACT in nucleosome reorganization and its relationship to DNA processes is well established, how these roles impact coordination in multicellular animal development are less well understood. Here we characterize the genes encoding FACT complex proteins in the nematode C...
October 15, 2018: Developmental Biology
Ki Hoon Han
HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions...
November 2018: Korean Circulation Journal
Yuki Hayashi, Junpei Yamaguchi, Toshio Kokuryo, Tomoki Ebata, Yukihiro Yokoyama, Masato Nagino
Although the regeneration of the adult liver depends on hepatic progenitor cells (HPCs), many uncertainties regarding hepatic regeneration in the injured liver remain. Trefoil factor family 1 (TFF1), a secretory protein predominantly expressed in the gastrointestinal tract, is responsible for mucosal restitution. Here, we investigated the role of TFF1 in liver regeneration using a mouse model of hepatic injury (choline-deficient ethionine-supplemented diet and carbon tetrachloride administration) and genetically engineered mice (TFF1 knockout (TFF1-/-))...
October 14, 2018: Biochemical and Biophysical Research Communications
Kenichi Watanabe, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Geetha Kandasamy, Meilei Harima, Ravichandiran Velayutham, Somasundaram Arumugam
Basidiomycetes-X (BDM-X) is a novel edible mushroom recently identified as a new fungi species and is effective against oxidative stress and anti-inflammation associated with immune response. However the effect of BDM-X on atopic dermatitis (AD) has not been elucidated. In this study, we have investigated the effect of BDM-X on AD skin lesions in NC/Nga mouse model. AD-like lesion was induced by the application of house dust mite extract (DfE) to the dorsal skin of NC/Nga mouse. After AD induction, BDM-X was administered once daily for 2 weeks...
October 9, 2018: Experimental and Molecular Pathology
Jihyun Park, Seonghyun Lee, Nabin Won, Eunji Shin, Soo-Hyun Kim, Min-Young Chun, Jungyeun Gu, Gun-Young Jung, Kwang-Il Lim, Kyubong Jo
The recent advances in the single cell genome analysis are generating a considerable amount of novel insights into complex biological systems. However, there are still technical challenges because each cell has a single copy of DNA to be amplified in most single cell genome analytical methods. In this paper, we present a novel approach to directly visualize a genomic map on a large DNA molecule instantly stained with red and green DNA-binding fluorescent proteins without DNA amplification. For this visualization, we constructed a few types of fluorescent protein-fused DNA-binding proteins: H-NS (histone-like nucleoid-structuring protein), DNA-binding domain of BRCA1 (breast cancer 1), high mobility group-1 (HMG), and lysine tryptophan (KW) repeat motif...
October 12, 2018: Analyst
Danai Chasioti, Xiaohui Yao, Pengyue Zhang, Samuel Lerner, Sara K Quinney, Xia Ning, Lang Li, Li Shen
Mining high-order drug-drug interaction (DDI) induced adverse drug effects from electronic health record (EHR) databases is an emerging area, and very few studies have explored the relationships between high-order drug combinations. We investigate a novel pharmacovigilance problem for mining directional DDI effects on myopathy using the FDA Adverse Event Reporting System (FAERS) database. Our work provides information on the risk of myopathy associated with adding new drugs on the already prescribed medication, and visualizes the identified directional DDI patterns as user-friendly graphical representation...
October 8, 2018: IEEE Journal of Biomedical and Health Informatics
Hangjun Zhang, Jianbo He, Ning Li, Nana Gao, Qiongxia Du, Bin Chen, Feifei Chen, Xiaodong Shan, Ying Ding, Weiqin Zhu, Yingzhu Wu, Juan Tang, Xiuying Jia
Perfluorooctanoic acid (PFOA) is a perfluorinated compound that is widely distributed, is persistent in the environment, and has a low-level chronic exposure effect on human health. The aim of this study was to investigate the peroxisome proliferator activated receptors γ (PPARγ) and the sterol regulatory element-binding protein 2 (SREBP2) signaling pathways in regulating the lipid damage response to PFOA in the livers of amphibians. Male and female frogs (Rana nigromaculata) were exposed to 0, 0.01, 0.1, 0...
October 4, 2018: Ecotoxicology and Environmental Safety
Shahla Korani, Mitra Korani, Samira Bahrami, Thomas P Johnston, Alexandra E Butler, Maciej Banach, Amirhossein Sahebkar
Hyperlipidemia is defined as an elevated level of lipids and lipoproteins in the blood and is considered to be a significant risk factor for accelerating the process of atherosclerosis and, consequently, cardiovascular disease. The level of cholesterol, especially low-density lipoprotein cholesterol (LDL-C), is commonly elevated in hyperlipidemia and represents the primary therapeutic target. Statins are a group of drugs that function by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and are extremely efficacious in reducing elevated LDL-C in the serum and preventing atherosclerotic cardiovascular disease...
October 5, 2018: Drug Discovery Today
M Cheurfa, H H Abdallah, R Allem, A Noui, C M N Picot-Allain, F Mahomoodally
Aqueous and ethanol extracts prepared from leaves of Olea europaea L. were evaluated for in vitro antioxidant and in vivo hypocholesterolemic effect. The result of administration of O. europaea leaf extracts on serum total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in hypercholesterolaemic mice was evaluated. In addition, rutin and luteolin, reported to occur naturally in O. europaea leaves, were docked against HMG-CoA reductase, the rate-limiting enzyme in cholesterol metabolism...
October 4, 2018: Food and Chemical Toxicology
Ibraheem Husain, Sana Khan, Saba Khan, Tushar Madaan, Sanjeev Kumar, Abul Kalam Najmi
Rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitor, and one of the most popular antihyperlipidemic medications has been found to possess pharmacodynamic activities much different from its usual indication. Recent research studies have revealed the efficacy of rosuvastatin in attenuating neuroinflammation, reducing the progression of Alzheimer's disease, providing protection against cerebral ischemia and spinal cord injury as well as ameliorating epilepsy. Mechanisms behind the neuroprotective potential of rosuvastatin can be attributed to its pleiotropic effects, independent of its ability to inhibit HMG-CoA reductase...
October 5, 2018: Clinical and Experimental Pharmacology & Physiology
Nidhi Malhotra, Yilin Qi, Nicholas A Spidale, Michela Frascoli, Bing Miu, Okhyun Cho, Katelyn Sylvia, Joonsoo Kang
Natural killer T (NKT) cells expressing the invariant T cell receptor (iTCR) serve an essential function in clearance of certain pathogens and have been implicated in autoimmune and allergic diseases. Complex effector programs of these iNKT cells are wired in the thymus, and upon thymic egress, they can respond within hours of antigenic challenges, classifying iNKT cells as innate-like. It has been assumed that the successful rearrangement of the invariant iTCRα chain is the central event in the divergence of immature thymocytes to the NKT cell lineage, but molecular properties that render the iTCR signaling distinct to permit the T cell lineage diversification remain obscure...
October 4, 2018: Journal of Experimental Medicine
Nicholas Theodosakis, Casey G Langdon, Goran Micevic, Irina Krykbaeva, Robert E Means, David F Stern, Marcus W Bosenberg
This study evaluates the use of HMG-CoA reducatase inhibitors, or statins, as an adjunctive to BRAF and MEK inhibition as a treatment in melanomas and other tumors with driver mutations in the MAPK pathway. Experiments used simvastatin in conjunction with vemurafenib and selumetinib in vitro and simvastatin with vemurafenib in vivo to demonstrated additional growth abrogation beyond MAPK blockade alone. Additional studies demonstrated that statin anti-tumor effects appeared to depend on inhibition of isoprenoid synthesis given rescue with add-back of downstream metabolites...
October 3, 2018: Pigment Cell & Melanoma Research
Jamuna Sankar, Ashokkumar Rathinavel, Sakeena Sadullah Mohammed Sadullah, Sivasitamparam Niranjali Devaraj
Dysregulated synthesis of hepatic cholesterol is a critical determinant of atherosclerosis. The combination of cholesterol and cholic acid (CC) diet supplementation to animal models is associated with hepatic dysfunction-mediated atherosclerosis. The current study was designed to investigate the hepatic cholesterol-lowering effects of oligomeric proanthocyanidins (OPC) in CC diet fed rats. CC diet-induced group exhibited significant increase in the hepatic lipid profile, activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), PON-1, LCAT, LPL, and LPO levels, and messenger RNA expression of HMGR, low-density lipoprotein receptor (LDLr), and HNF-4α...
October 1, 2018: Journal of Biochemical and Molecular Toxicology
Loraine De Jesús Quintana-Pájaro, Yancarlos Ramos-Villegas, Eileen Cortecero-Sabalza, Andrei F Joaquim, Amit Agrawal, Alexis Rafael Narvaez-Rojas, Luis Rafael Moscote-Salazar
Background and Objectives: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, used for the management of hypercholesterolemia and related atherosclerotic diseases. Several studies have indicated the neuroprotective effects of statins on several neuropathological conditions. However, the role of these medications in epilepsy is still unclear. The purpose is to evaluate and summarize the level of evidence on the efficacy of statins in neuronal hyperexcitability and the neuroinflammatory processes of epilepsy...
October 2018: Journal of Neurosciences in Rural Practice
Patrik Brundin, Richard K Wyse
The Linked Clinical Trials (LCT) initiative is a drug repurposing program specifically aimed at identifying drugs that can slow the progression of Parkinson's disease (PD). Tom Isaacs was one of the key people behind the idea of LCT in 2011. He ensured it became a priority of The Cure Parkinson's Trust (CPT), a philanthropic funding body based in the UK which Tom had co-founded 7 years earlier. During the latter six years of his life, Tom Isaacs was heavily involved in the LCT initiative and held the program dear to his heart...
September 30, 2018: European Journal of Neuroscience
Xiaohua Xia, Ruyan Wan, Weiran Huo, Linxia Zhang, Xiaopei Xia, Zhongjie Chang
Sox4 , a member of the SoxC subfamily which of the Sox family, plays important roles in the development of the vertebrate gonad and nervous system. We have cloned a Sox4 homologue fromthe brain of Misgurnus anguillicaudatus using homologous cloning and rapid amplification of cDNA ends. We named the cloned gene as MaSox4 . The full-length cDNA was 2122 bp, containing a 718 bp 5'-untranslated region and a 267 bp 3'-untranslated region. The open-reading frame of the cloned gene encoded 378 amino acids and contained a characteristic HMG-box DNA-binding domain with the specific motif (RPMNAFMVW)...
September 2018: Journal of Genetics
Wazir Abdullahi, Hrvoje Brzica, Nicholas A Hirsch, Bianca G Reilly, Patrick T Ronaldson
Central nervous system (CNS) drug delivery can be achieved by targeting drug uptake transporters such as organic anion transporting polypeptide (Oatp)-1a4. In fact, many drugs that can improve neurological outcomes in CNS diseases (i.e., HMG-CoA reductase inhibitors (i.e., statins)) are Oatp transport substrates. To date, transport properties and regulatory mechanisms of Oatp1a4 at the BBB have not been rigorously studied. Such knowledge is critical to develop Oatp1a4 for optimization of CNS drug delivery and for improved treatment of CNS diseases...
September 27, 2018: Molecular Pharmacology
Iwona Patyk, Cezary Rybacki, Agata Kalicka, Agnieszka Rzeszotarska, Jolanta Korsak, Andrzej Chciałowski
Chronic obstructive pulmonary disease (COPD) is a progressive disease underlain by airway inflammation. Despite trials with new generations of anti-inflammatory drugs to alleviate the disease burden, the effective curative treatment remains elusive. In this context, the aim of this study was to assess the influence of simvastatin, a leading member of the family of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known to display anti-inflammatory and immunomodulatory activity, on symptoms and lung function, as well as the proportion of inflammatory cells, cytokines, proteolytic enzymes, and surfactant protein D (SP-D) content in bronchoalveolar lavage fluid (BALF) in COPD patients...
September 26, 2018: Advances in Experimental Medicine and Biology
Ayano Funamizu, Atsushi Fukui, Rie Fukuhara, Asami Kobayashi, Hitomi Chiba, Yukiko Matsumura, Asami Ito, Hideki Mizunuma
Bilateral tubal pregnancy is very rare and occurs in only 1 out of every 200,000 spontaneous pregnancies. In this case, a 29-year-old woman with a history of primary infertility underwent treatment with human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG), and became pregnant. A gestational sac (GS) was not detected in the uterus and transvaginal ultrasonography (USG) revealed GS with fetal heartbeat in the left adnexa at 7 weeks and 6 days of gestation. The patient underwent laparoscopic surgery and ultimately, bilateral tubal pregnancy was diagnosed...
October 2017: Gynecology and minimally invasive therapy
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