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1.
Role of ACE2-Ang (1-7)-Mas axis in post-COVID-19 complications and its dietary modulation.
Sahu, S, Patil, CR, Kumar, S, Apparsundaram, S, Goyal, RK
Molecular and cellular biochemistry. 2022;(1):225-240
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Abstract
Severe acute respiratory syndrome-coronavirus-2 (COVID-19) virus uses Angiotensin-Converting Enzyme 2 (ACE2) as a gateway for their entry into the human body. The ACE2 with cleaved products have emerged as major contributing factors to multiple physiological functions and pathogenic complications leading to the clinical consequences of the COVID-19 infection Decreased ACE2 expression restricts the viral entry into the human cells and reduces the viral load. COVID-19 infection reduces the ACE2 expression and induces post-COVID-19 complications like pneumonia and lung injury. The modulation of the ACE2-Ang (1-7)-Mas (AAM) axis is also being explored as a modality to treat post-COVID-19 complications. Evidence indicates that specific food components may modulate the AAM axis. The variations in the susceptibility to COVID-19 infection and the post-COVID its complications are being correlated with varied dietary habits. Some of the food substances have emerged to have supportive roles in treating post-COVID-19 complications and are being considered as adjuvants to the COVID-19 therapy. It is possible that some of their active ingredients may emerge as the direct treatment for the COVID-19.
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2.
CLAVATA3, a plant peptide controlling stem cell fate in the meristem.
Hirakawa, Y
Peptides. 2021;:170579
Abstract
CLAVATA3 (CLV3) is a peptide signal initially identified in the analysis of clv mutants in the model plant Arabidopsis thaliana, as a regulator of meristem homeostasis and floral organ numbers. CLV3 homologs are widely conserved in land plants, collectively called CLV3/ESR-related (CLE) genes. A 12-amino acid CLE peptide with hydroxyproline residues was identified in Zinnia elegans cell culture system, in which cells secrete a CLE peptide called tracheary element differentiation factor (TDIF) into the culture medium. Mature CLV3 peptide is also a post-translationally modified short peptide containing additional triarabinosylation on a hydroxyproline residue. Genetic studies have revealed the involvement of leucin-rich repeat receptor-like kinases (LRR-RLKs) in CLV3 signaling, including CLV1/BAM-CIK, CLV2-CRN and RPK2, although the mechanisms of signal transduction and integration via crosstalk is still largely unknown. Recent studies on bryophyte model species provided a clue to understand evolution and ancestral function of CLV signaling in land plants. Fundamental understanding on CLV signaling provided an opportunity to optimize the crop yield traits using a novel breeding technology with CRISPR/Cas genome editing.
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3.
Plant-derived peptides improving lipid and glucose metabolism.
Nagaoka, S, Takeuchi, A, Banno, A
Peptides. 2021;:170577
Abstract
Plant protein-derived peptides, focusing especially on soybean protein-derived peptides have considerable effects on metabolic regulation and modulation such as cholesterol lowering, triglyceride lowering, anti-obesity, inhibition of fatty acid synthase, and antidiabetic effects. The molecules targeted to study the metabolic regulatory functions of the peptides included the following: intestinal cholesterol micelle, cholesterol metabolism-related genes for cholesterol lowering, triglyceride metabolism-related genes for triglyceride lowering and anti-obesity, dipeptidyl peptidase-IV (DPP-IV), α-amylase, α-glucosidase, or glucose metabolism-related genes for lowering blood glucose levels. This review article outlines the physiological functions of plant protein-derived peptides for the improvement of lipid and glucose metabolism in vitro or in vivo.
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4.
Risk of heart failure progression in patients with reduced ejection fraction: mechanisms and therapeutic options.
Gronda, E, Vanoli, E, Sacchi, S, Grassi, G, Ambrosio, G, Napoli, C
Heart failure reviews. 2020;(2):295-303
Abstract
Transition from stage C to stage D of heart failure (HF) represents an irreversible process toward end-stage disease. Crucial interventions to be adopted in the attempt to interfere with this process are represented by the identification of patients at high risk to develop HF progression and by an effective and prompt management. Markers of worse prognosis and disease progression are well established and include recurrence of HF decompensation, intolerance to the neurohormonal standard pharmacological treatment, and resistance to loop diuretics. In addition, both NT-proBNP and sympathetic nervous system (SNS) overdrive are strong predictors of adverse clinical outcome and allow to identify high-risk HF patients even in the presence of mild symptoms. To counteract the deleterious effects of the SNS activation, new strategies such as a new drug combining angiotensin receptor and neprilysin inhibition and baroreceptor stimulation therapy (BAT) have been investigated. Inability to properly counteract the SNS overdrive leads to acute HF decompensation by different mechanisms. The leading ones are represented by the progressive sodium and water retention with fluid overload and by the blood volume redistribution between splanchnic and non-splanchnic regions. The correct understanding of these mechanisms, together with the availability of new therapeutic options such as peritoneal ultrafiltration, represent the rationale but not infrequently overlooked therapeutic options to improve congestion management in HF patients.
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5.
Glycomacropeptide: long-term use and impact on blood phenylalanine, growth and nutritional status in children with PKU.
Daly, A, Evans, S, Chahal, S, Santra, S, Pinto, A, Jackson, R, Gingell, C, Rocha, J, Van Spronsen, FJ, MacDonald, A
Orphanet journal of rare diseases. 2019;(1):44
Abstract
UNLABELLED In phenylketonuria, casein glycomacropeptide (CGMP) requires modification with the addition of some essential and semi essential amino acids to ensure suitability as a protein substitute. The optimal amount and ratio of additional amino acids is undefined. AIM: A longitudinal, parallel, controlled study over 12 months evaluating a CGMP (CGMP-AA2) formulation compared with phenylalanine-free L-amino acid supplements (L-AA) on blood Phe, Tyr, Phe:Tyr ratio, biochemical nutritional status and growth in children with PKU. The CGMP-AA2 contained 36 mg Phe per 20 g protein equivalent. METHODS Children with PKU, with a median age of 9.2 y (5-16y) were divided into 2 groups: 29 were given CGMP-AA2, 19 remained on Phe-free L-AA. The CGMP-AA2 formula gradually replaced L-AA, providing blood Phe concentrations were maintained within target range. Median blood Phe, Tyr, Phe:Tyr ratio and anthropometry, were compared within and between the two groups at baseline, 26 and 52 weeks. Nutritional biochemistry was studied at baseline and 26 weeks only. RESULTS At the end of 52 weeks only 48% of subjects were able to completely use CGMP-AA2 as their single source of protein substitute. At 52 weeks CGMP-AA2 provided a median of 75% (30-100) of the total protein substitute with the remainder being given as L-AA. Within the CGMP-AA2 group, blood Phe increased significantly between baseline and 52 weeks: [baseline to 26 weeks; baseline Phe 270 μmol/L (170-430); 26 weeks, Phe 300 μmol/L (125-485) p = 0.06; baseline to 52 weeks: baseline, Phe 270 μmol/L (170-430), 52 weeks Phe 300 μmol/L (200-490), p < 0.001)]. However, there were no differences between the CGMP-AA2 and L-AA group for Phe, Tyr, Phe:Tyr ratio or anthropometry at any of the three measured time points. Within the CGMP-AA2 group only weight (p = 0.0001) and BMI z scores (p = 0.0001) increased significantly between baseline to 52 weeks. Whole blood and plasma selenium were significantly higher (whole blood selenium [p = 0.0002]; plasma selenium [p = 0.0007]) at 26 weeks in the CGMP-AA2 group compared L-AA. No differences were observed within the L-AA group for any of the nutritional markers. CONCLUSIONS CGMP-AA increases blood Phe concentrations and so it can only be used partly to contribute to protein substitute in some children with PKU. CGMP-AA should be carefully introduced in children with PKU and close monitoring of blood Phe control is essential.
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Bivalirudin during percutaneous coronary intervention in acute coronary syndromes.
Laine, M, Lemesle, G, Dabry, T, Panagides, V, Peyrol, M, Paganelli, F, Bonello, L
Expert opinion on pharmacotherapy. 2019;(3):295-304
Abstract
INTRODUCTION Anticoagulant therapy is critical to prevent ischemic recurrences and complications in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Unfractionated heparin (UFH), an injectable anticoagulant has several limitations: lack of predictability of its biological efficacy, platelets activation, heparin-induced thrombopenia and bleedings. Bivalirudin, a synthetic direct thrombin inhibitor has biological properties that promised better clinical outcome in ACS patients undergoing PCI. AREAS COVERED The present review aimed to summarize two decades of randomized clinical trials that compared bivalirudin to UFH in ACS patients treated with PCI. Early trials highlighted a reduction of bleedings with bivalirudin compared to UFH in combination with glycoprotein inhibitors (GPI). Recent studies questioned this reduction given that GPI are less and less used during PCI. Further, trials raised concerns about the risk of stent thrombosis in patients treated with bivalirudin. In light of this data, bivalirudin has been downgraded in international guidelines and appears as a second line anticoagulant agent after UFH. EXPERT OPINION The highly questioned reduction of bleedings under bivalirudin and the potential risk of stent thrombosis are unwarranted. Based on clinical trials, UFH has no equivalent in terms of anticoagulation in ACS patients undergoing PCI.
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7.
An overview of glutaminyl cyclase inhibitors for Alzheimer's disease.
Coimbra, JR, Sobral, PJ, Santos, AE, Moreira, PI, Salvador, JA
Future medicinal chemistry. 2019;(24):3179-3194
Abstract
A diverse range of N-terminally truncated and modified forms of amyloid-β (Aβ) oligomers have been discovered in Alzheimer's disease brains, including the pyroglutamate-Aβ (AβpE3). AβpE3 species are shown to be more neurotoxic when compared with the full-length Aβ peptide. Findings visibly suggest that glutaminyl cyclase (QC) catalyzed the generation of cerebral AβpE3, and therapeutic effects are achieved by reducing its activity. In recent years, efforts to effectively develop QC inhibitors have been pursued worldwide. The inhibitory activity of current QC inhibitors is mainly triggered by zinc-binding groups that coordinate Zn2+ ion in the active site and other common features. Herein, we summarized the current state of discovery and evolution of QC inhibitors as a potential Alzheimer's disease-modifying strategy.
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8.
Electrochemistry of Alzheimer Disease Amyloid Beta Peptides.
Chiorcea-Paquim, AM, Enache, TA, Oliveira-Brett, AM
Current medicinal chemistry. 2018;(33):4066-4083
Abstract
Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterization. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation are electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates, protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, particularly zinc, copper and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed.
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9.
Biased selection of propagation-related TUPs from phage display peptide libraries.
Zade, HM, Keshavarz, R, Shekarabi, HSZ, Bakhshinejad, B
Amino acids. 2017;(8):1293-1308
Abstract
Phage display is rapidly advancing as a screening strategy in drug discovery and drug delivery. Phage-encoded combinatorial peptide libraries can be screened through the affinity selection procedure of biopanning to find pharmaceutically relevant cell-specific ligands. However, the unwanted enrichment of target-unrelated peptides (TUPs) with no true affinity for the target presents an important barrier to the successful screening of phage display libraries. Propagation-related TUPs (Pr-TUPs) are an emerging but less-studied category of phage display-derived false-positive hits that are displayed on the surface of clones with faster propagation rates. Despite long regarded as an unbiased selection system, accumulating evidence suggests that biopanning may create biological bias toward selection of phage clones with certain displayed peptides. This bias can be dependent on or independent of the displayed sequence and may act as a major driving force for the isolation of fast-growing clones. Sequence-dependent bias is reflected by censorship or over-representation of some amino acids in the displayed peptide and sequence-independent bias is derived from either point mutations or rare recombination events occurring in the phage genome. It is of utmost interest to clean biopanning data by identifying and removing Pr-TUPs. Experimental and bioinformatic approaches can be exploited for Pr-TUP discovery. With no doubt, obtaining deeper insight into how Pr-TUPs emerge during biopanning and how they could be detected provides a basis for using cell-targeting peptides isolated from phage display screening in the development of disease-specific diagnostic and therapeutic platforms.
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10.
CSF Aβ1-42 - an excellent but complicated Alzheimer's biomarker - a route to standardisation.
Kuhlmann, J, Andreasson, U, Pannee, J, Bjerke, M, Portelius, E, Leinenbach, A, Bittner, T, Korecka, M, Jenkins, RG, Vanderstichele, H, et al
Clinica chimica acta; international journal of clinical chemistry. 2017;:27-33
Abstract
The 42 amino acid form of amyloid β (Aβ1-42) in cerebrospinal fluid (CSF) has been widely accepted as a central biomarker for Alzheimer's disease. Several immunoassays for CSF Aβ1-42 are commercially available, but can suffer from between laboratory and batch-to-batch variability as well as lack of standardisation across assays. As a consequence, no general cut-off values have been established for a specific context of use (e.g., clinical diagnostics) and selection of individuals for enrolment in clinical trials (patient stratification) remains challenging. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has initiated a working group for CSF proteins (WG-CSF) to facilitate standardisation of CSF Aβ1-42 measurement results. The efforts of the IFCC WG-CSF include the development of certified reference materials (CRMs) and reference measurement procedures (RMPs) for key biomarkers. Two candidate RMPs for quantification of Aβ1-42 in CSF based on liquid chromatography tandem mass spectrometry have been developed and tested in two ring trials. Furthermore, two commutability studies including native CSF pools, artificial CSF and spiked materials have been completed. On the basis of these studies, human CSF pools containing only endogenous Aβ1-42 at three concentrations were selected as the format for future CRMs that are now being processed.