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heme review

Paulina Podkalicka, Olga Mucha, Jozef Dulak, Agnieszka Loboda
Duchenne muscular dystrophy (DMD) represents one of the most devastating types of muscular dystrophies which affect boys already at early childhood. Despite the fact that the primary cause of the disease, namely the lack of functional dystrophin is known already for more than 30 years, DMD still remains an incurable disease. Thus, an enormous effort has been made during recent years to reveal novel mechanisms that could provide therapeutic targets for DMD, especially because glucocorticoids treatment acts mostly symptomatic and exerts many side effects, whereas the effectiveness of genetic approaches aiming at the restoration of functional dystrophin is under the constant debate...
February 15, 2019: Cellular and Molecular Life Sciences: CMLS
Bruce Wang, Sean Rudnick, Brent Cengia, Herbert L Bonkovsky
The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Recent results indicate that acute intermittent porphyria, the most severe of the more common types of AHP, is more prevalent than previously thought, occurring in about 1 in 1600 Caucasians, but with low clinical penetrance (approximately 2%-3%)...
February 2019: Hepatology Communications
Kazuo Kobayashi
Pulse radiolysis is a powerful method for generating highly reduced or oxidized species and free radicals. Combined with fast time-resolved spectroscopic measurement, we can monitor the reactions of intermediate species on time scales ranging from picoseconds to seconds. The application of pulse radiolysis to water generates hydrated electrons (eaq - ) and specific radicals, rendering this technique useful for investigating a number of biological redox processes. The first pulse radiolysis redox investigations explored in this review involved intramolecular electron transfer processes in protein with multiple electron-accepting sites...
February 11, 2019: Chemical Reviews
Vance G Nielsen, Nathaniel Frank, Sam Afshar
Snakebite with hemotoxic venom continues to be a major source of morbidity and mortality worldwide. Our laboratory has characterized the coagulopathy that occurs in vitro in human plasma via specialized thrombelastographic methods to determine if venoms are predominantly anticoagulant or procoagulant in nature. Further, the exposure of venoms to carbon monoxide (CO) or O -phenylhydroxylamine (PHA) modulate putative heme groups attached to key enzymes has also provided mechanistic insight into the multiple different activities contained in one venom...
February 6, 2019: Toxins
Emily Hanson, Mark Sheldon, Brenda Pacheco, Mohammed Alkubeysi, Veena Raizada
Friedreich's ataxia (FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical manifestations of FRDA include ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases. However, the broad clinical spectrum makes FRDA difficult to identify. The diagnosis of FRDA is based on the presence of suspicious clinical factors, the use of the Harding criteria and, more recently, the use of genetic testing for identifying the expansion of a triplet nucleotide sequence...
January 26, 2019: World Journal of Cardiology
Jin-Fu Zhou, Jin-Ying Luo, Wen-Bin Zhu, Chang-Yi Yang, Ying-Lin Zeng, Xiao-Long Qiu
OBJECTIVE: The association between a (GT)n dinucleotide length polymorphism in the promoter region of heme oxygenase 1 (HMOX1) and the risk of neonatal hyperbilirubinemia remains controversial. This meta-analysis was, therefore, performed with aims to examine the correlation between the HMOX1 (GT)n repeat length polymorphism and neonatal hyperbilirubinemia susceptibility. MATERIALS AND METHODS: We searched the databases including PubMed, Embase, Cochrane Library, China national knowledge infrastructure (CNKI), and Wanfang Data, with all reviewed studies published before 28 June 2018...
January 30, 2019: Journal of Maternal-fetal & Neonatal Medicine
Vicente Gotor-Fernández, Caroline E Paul
Deep eutectic solvents (DES) are a class of neoteric solvents used in multiple applications amongst which biocatalytic processes. Due to its simple preparation, low cost and inherent biodegradable properties, its use as a non-volatile biocompatible co-solvent with both whole cells and isolated enzymes has displayed increased enzyme activity and stability translating to higher product conversions and a surprising higher enantioselectivity in a range of biotransformations. This review lays out the latest updates on the use of DES in redox biocatalytic reactions...
January 26, 2019: Journal of Biotechnology
Peter Sandner, Daniel P Zimmer, G Todd Milne, Markus Follmann, Adrian Hobbs, Johannes-Peter Stasch
When Furchgott, Murad, and Ignarro were honored with the Nobel prize for the identification of nitric oxide (NO) in 1998, the therapeutic implications of this discovery could not be fully anticipated. This was due to the fact that available therapeutics like NO donors did not allow a constant and long-lasting cyclic guanylyl monophosphate (cGMP) stimulation and had a narrow therapeutic window. Now, 20 years later, the stimulator of soluble guanylate cyclase (sGC), riociguat, is on the market and is the only drug approved for the treatment of two forms of pulmonary hypertension (PAH/CTEPH), and a variety of other sGC stimulators and sGC activators are in preclinical and clinical development for additional indications...
January 29, 2019: Handbook of Experimental Pharmacology
K Mahmoudi, K L Garvey, A Bouras, G Cramer, H Stepp, J G Jesu Raj, D Bozec, T M Busch, C G Hadjipanayis
INTRODUCTION: Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells. MATERIALS/METHODS: A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs)...
January 18, 2019: Journal of Neuro-oncology
Crystal D Karakochuk, Sonja Y Hess, Denish Moorthy, Sorrel Namaste, Megan E Parker, Aviva I Rappaport, Rita Wegmüller, Omar Dary
Anemia affects over 800 million women and children globally. Defined as a limited or insufficient functional red blood cell supply in peripheral blood, anemia causes a reduced oxygen supply to tissues and can have serious health consequences for women and children. Hemoglobin (Hb) concentration is most commonly measured for anemia diagnosis. Methods to measure Hb are usually invasive (requiring a blood sample); however, advances in diagnostic and clinical chemistry over the past decade have led to the development of new noninvasive methods...
January 16, 2019: Annals of the New York Academy of Sciences
Mattis Bekkelund, Dag A Sangnes, Jan Gunnar Hatlebakk, Lars Aabakken
OBJECTIVES: Idiopathic gastroparesis is a gastric motility disorder characterized by chronic upper gastrointestinal symptoms and delayed gastric emptying without an identifiable underlying condition. This review summarizes recent understanding of the pathophysiology and treatment of idiopathic gastroparesis. MATERIALS AND METHODS: Structured literature search in the PubMed, Embase and databases. RESULTS: Idiopathic gastroparesis involves several alterations in gastric motility and sensation, including delayed gastric emptying, altered myoelectrical activity, impaired fundic accommodation, visceral hypersensitivity and disturbances in antropyloroduodenal motility and coordination...
January 13, 2019: Scandinavian Journal of Gastroenterology
Arianna Sasso, Giovanni Latella
The growing incidence of colorectal cancer (CRC) in the world seems to be related to the spread of Westernized lifestyles, particularly dietary habits. Several studies have found that high consumption of red meat-especially processed red meat, a mainstay of Western diets-is associated with an increased risk of developing CRC. One possible reason for the association are the adverse effects exerted by the heme iron contained in red meat, which has the potential to affect homeostasis and colonic epithelial cell renewal and to promote the formation of mutagenic and carcinogenic agents...
January 14, 2019: Nutrition and Cancer
Kshatresh Dutta Dubey, Sason Shaik
This Account addresses the catalytic cycle of the enzyme cytochrome P450 (CYP450) as a prototypical biological machine with automatic features. CYP450 is a nanomachine that uses dioxygen and two reducing and two proton equivalents to oxidize a plethora of molecules (so-called substrates) as a means of supplying bio-organisms with essential molecules (e.g., brain neurotransmitters, sex hormones, etc.) and protecting biosystems against poisoning. An enticing property of CYP450s is that entrance of an oxidizable substrate into the active site initiates a series of events that constitute the catalytic cycle, which functions "automatically" in a regulated sequence of events culminating in the production of the oxidized substrates (e...
January 11, 2019: Accounts of Chemical Research
Mitchell Reitsma, John Fox, Pierre Vanden Borre, Matthew Cavanaugh, Yakov Chudnovsky, Rachel L Erlich, Thomas E Gribbin, Rachel Anhorn
BACKGROUND: Comprehensive genomic profiling (CGP) is a next-generation sequencing-based methodology that detects 4 classes of genomic alterations, as well as gene signature biomarkers such as microsatellite instability and tumor mutational burden. In the context of precision oncology, CGP can help to direct treatment to genomically matched therapies. OBJECTIVE: To describe the results of a 3-year observational analysis of patients undergoing testing with CGP assays (either FoundationOne or FoundationOne Heme) at a community oncology practice after a regional health plan implemented a medical policy that enabled coverage of CGP...
January 11, 2019: Journal of Managed Care & Specialty Pharmacy
Stavros Topouzis, Garyfallia I Makrynitsa, Aikaterini A Zompra, Aikaterini I Argyriou, Georgios A Spyroulias
The soluble guanylate cyclase (sGC) is the physiological sensor for nitric oxide and alterations of its function are actively implicated in a wide variety of pathophysiological conditions. Intense research efforts over the past 20 years have provided significant information on its regulation, culminating in the rational development of approved drugs or investigational lead molecules, which target and interact with sGC through novel mechanisms. However, there are numerous questions that remain unanswered. Ongoing investigations, with the critical aid of structural chemistry studies, try to further elucidate the enzyme's structural characteristics that define the association of "stimulators" or "activators" of sGC in the presence of absence of the heme moiety, respectively, as well as the precise conformational attributes that will allow the design of more innovative and effective drugs...
January 7, 2019: Current Medicinal Chemistry
Rachel Golonka, Beng San Yeoh, Matam Vijay-Kumar
Iron is necessary for the survival of almost all aerobic organisms. In the mammalian host, iron is a required cofactor for the assembly of functional iron-sulfur (Fe-S) cluster proteins, heme-binding proteins and ribonucleotide reductases that regulate various functions, including heme synthesis, oxygen transport and DNA synthesis. However, the bioavailability of iron is low due to its insolubility under aerobic conditions. Moreover, the host coordinates a nutritional immune response to restrict the accessibility of iron against potential pathogens...
January 3, 2019: Journal of Innate Immunity
Hiroshi Kobayashi, Yuki Yamada, Naoki Kawahara, Kenji Ogawa, Chiharu Yoshimoto
In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations...
December 21, 2018: Oncology Reports
Huiju Lee, Yoon Kyung Choi
Heme oxygenase (HO) catabolizes heme to produce HO metabolites, such as carbon monoxide (CO) and bilirubin (BR), which have gained recognition as biological signal transduction effectors. The neurovascular unit refers to a highly evolved network among endothelial cells, pericytes, astrocytes, microglia, neurons, and neural stem cells in the central nervous system (CNS). Proper communication and functional circuitry in these diverse cell types is essential for effective CNS homeostasis. Neuroinflammation is associated with the vascular pathogenesis of many CNS disorders...
December 25, 2018: International Journal of Molecular Sciences
Shih-Kai Chiang, Shuen-Ei Chen, Ling-Chu Chang
Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases...
December 21, 2018: International Journal of Molecular Sciences
Meng Wang, Li-Juan Ma, Yan Yang, Zeyu Xiao, Jian-Bo Wan
Excess alcohol exposure leads to alcoholic liver disease (ALD), a predominant cause of liver-related morbidity and mortality worldwide. In the past decade, increasing attention has been paid to understand the association between n-3 polyunsaturated fatty acids (n-3 PUFAs) and ALD. In this review, we summarize the metabolism of n-3 PUFAs, animal model of ALD, and the findings from recent studies determining the role of n-3 PUFAs in ALD as a possible treatment. The animal models of acute ethanol exposure, chronic ethanol exposure and chronic-plus-single binge ethanol feeding have been widely used to explore the impact of n-3 PUFAs...
December 22, 2018: Critical Reviews in Food Science and Nutrition
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