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A Promising Candidate: Heparin-Binding Protein Steps onto the Stage of Sepsis Prediction.
Yang, Y, Liu, G, He, Q, Shen, J, Xu, L, Zhu, P, Zhao, M
Journal of immunology research. 2019;:7515346
Abstract
Sepsis is a systemic inflammatory response syndrome caused by infection. With high morbidity and mortality of this disease, there is a need to find early effective diagnosis and assessment methods to improve the prognosis of patients. Heparin-binding protein (HBP) is a granular protein derived from polynuclear neutrophils. The biosynthetic HBP in neutrophils is rapidly released under the stimulation of bacteria, resulting in increased vascular permeability and edema. It is reasonable to speculate that the HBP in plasma may serve as a novel diagnostic marker for sepsis, bacterial skin infection, acute bacterial meningitis, leptospirosis, protozoan parasites, and even some noncommunicable diseases. It implies that in the detection and diagnosis of sepsis, it will be possible to make relevant diagnosis through this new indicator in the future. In this review, we summarize the typical biological function of HBP and its latest research progress to provide theoretical basis for clinical prediction and diagnosis of sepsis.
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Current understanding of the gut microbiota shaping mechanisms.
Chang, CS, Kao, CY
Journal of biomedical science. 2019;(1):59
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Increasing evidences have shown strong associations between gut microbiota and many human diseases, and understanding the dynamic crosstalks of host-microbe interaction in the gut has become necessary for the detection, prevention, or therapy of diseases. Many reports have showed that diet, nutrient, pharmacologic factors and many other stimuli play dominant roles in the modulation of gut microbial compositions. However, it is inappropriate to neglect the impact of host factors on shaping the gut microbiota. In this review, we highlighted the current findings of the host factors that could modulate the gut microbiota. Particularly the epithelium-associated factors, including the innate immune sensors, anti-microbial peptides, mucus barrier, secretory IgAs, epithelial microvilli, epithelial tight junctions, epithelium metabolism, oxygen barrier, and even the microRNAs are discussed in the context of the microbiota shaping. With these shaping factors, the gut epithelial cells could select the residing microbes and affect the microbial composition. This knowledge not only could provide the opportunities to better control many diseases, but may also be used for predicting the success of fecal microbiota transplantation clinically.
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Cooperative interaction of antimicrobial peptides with the interrelated immune pathways in plants.
Bolouri Moghaddam, MR, Vilcinskas, A, Rahnamaeian, M
Molecular plant pathology. 2016;(3):464-71
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Plants express a diverse repertoire of functionally and structurally distinct antimicrobial peptides (AMPs) which provide innate immunity by acting directly against a wide range of pathogens. AMPs are expressed in nearly all plant organs, either constitutively or in response to microbial infections. In addition to their direct activity, they also contribute to plant immunity by modulating defence responses resulting from pathogen-associated molecular pattern/effector-triggered immunity, and also interact with other AMPs and pathways involving mitogen-activated protein kinases, reactive oxygen species, hormonal cross-talk and sugar signalling. Such links among AMPs and defence signalling pathways are poorly understood and there is no clear model for their interactions. This article provides a critical review of the empirical data to shed light on the wider role of AMPs in the robust and resource-effective defence responses of plants.
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Autophagy as a target for therapeutic uses of multifunctional peptides.
Muciño, G, Castro-Obregón, S, Hernandez-Pando, R, Del Rio, G
IUBMB life. 2016;(4):259-67
Abstract
The emergence of complex diseases is promoting a change from one-target to multitarget drugs and peptides are ideal molecules to fulfill this polypharmacologic role. Here we review current status in the design of polypharmacological peptides aimed to treat complex diseases, focusing on tuberculosis. In this sense, combining multiple activities in single molecules is a two-sided sword, as both positive and negative side effects might arise. These polypharmacologic compounds may be directed to regulate autophagy, a catabolic process that enables cells to eliminate intracellular microbes (xenophagy), such as Mycobacterium tuberculosis (MBT). Here we review some strategies to control MBT infection and propose that a peptide combining both antimicrobial and pro-autophagic activities would have a greater potential to limit MBT infection. This endeavor may complement the knowledge gained in understanding the mechanism of action of antibiotics and may lead to the design of better polypharmacological peptides to treat complex diseases such as tuberculosis.
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Hepcidin and iron regulation in health and disease.
Means, RT
The American journal of the medical sciences. 2013;(1):57-60
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A decade ago, hepcidin, an antimicrobial peptide with iron-regulatory properties, was discovered and proposed as playing a significant role in the pathogenesis of anemia of chronic disease. Subsequent studies have demonstrated that hepcidin is the keystone of the linked systems of iron balance and iron transport in health and in disease. The definition of the role of hepcidin and its regulation has permitted the mechanisms of disorders of iron homeostasis to be understood at a molecular level. Future studies may identify roles for hepcidin or hepcidin-related molecules in diagnosis and therapy.
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Should we reconsider iron administration based on prevailing ferritin and hepcidin concentrations?
Nakanishi, T, Kuragano, T, Kaibe, S, Nagasawa, Y, Hasuike, Y
Clinical and experimental nephrology. 2012;(6):819-26
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The results of recent randomized, controlled trials in patients with chronic kidney disease and anemia have suggested that hyporesponsiveness to erythropoiesis stimulating agents (ESA) is a significant predictor of poor patient outcomes. Functional iron deficiency (FID) is the most common cause of suboptimal ESA response, and intravenous iron administration (IVFe) efficiently raises hemoglobin (Hb) concentrations even under the condition of FID. Consequently, renal anemia correction has conceptually shifted from 'higher Hb values with high ESA doses' to 'prevention of ESA hyporesponsiveness with IVFe'. The discovery of hepcidin has profoundly changed our understanding of the place of FID in renal anemia therapy. Hepcidin reduces the abundance of iron transport proteins which facilitate iron absorption from the gut and iron mobilization from macrophages. Serum hepcidin is mainly modulated by iron stores, as is serum ferritin. High hepcidin or ferritin levels block intestinal iron absorption and iron recycling in macrophages and decrease iron availability for erythropoiesis, leading to FID. Iron administration, especially IVFe, increases hepcidin levels and concomitantly inhibits iron supply to erythroid cells. This in turn could lead to a vicious circle, exacerbating FID and increasing iron demand. Therefore, physicians should be cautious with unrestricted IVFe to chronic kidney disease patients with FID.
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[Iron metabolism and maternal-fetal iron circulation].
Słomka, A, Zekanowska, E, Piotrowska, K, Kwapisz, J
Postepy higieny i medycyny doswiadczalnej (Online). 2012;:876-87
Abstract
Iron is an essential micronutrient for the proper functioning of most organisms. This element is used in oxygen transport, myelin and neurotransmitters synthesis, cell cycle and synthesis of nucleic acids. The importance of iron in the maturation of lymphocytes and proper functioning of the eye is also stressed. Newborns are particularly sensitive to imbalances in iron metabolism. Iron deficiency during pregnancy carries serious clinical consequences. It seems that a key role in the transport of iron between mother and fetus is plays by hepcidin and, described in 2010 zyklopen. The physiological role of proteins involved in iron metabolism and transport of this metal by the placenta are described in this paper.
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Hereditary hemochromatosis and transferrin receptor 2.
Chen, J, Enns, CA
Biochimica et biophysica acta. 2012;(3):256-63
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BACKGROUND Multicellular organisms regulate the uptake of calories, trace elements, and other nutrients by complex feedback mechanisms. In the case of iron, the body senses internal iron stores, iron requirements for hematopoiesis, and inflammatory status, and regulates iron uptake by modulating the uptake of dietary iron from the intestine. Both the liver and the intestine participate in the coordination of iron uptake and distribution in the body. The liver senses inflammatory signals and iron status of the organism and secretes a peptide hormone, hepcidin. Under high iron or inflammatory conditions hepcidin levels increase. Hepcidin binds to the iron transport protein, ferroportin (FPN), promoting FPN internalization and degradation. Decreased FPN levels reduce iron efflux out of intestinal epithelial cells and macrophages into the circulation. Derangements in iron metabolism result in either the abnormal accumulation of iron in the body, or in anemias. The identification of the mutations that cause the iron overload disease, hereditary hemochromatosis (HH), or iron-refractory iron-deficiency anemia has revealed many of the proteins used to regulate iron uptake. SCOPE OF THE REVIEW In this review we discuss recent data concerning the regulation of iron homeostasis in the body by the liver and how transferrin receptor 2 (TfR2) affects this process. MAJOR CONCLUSIONS TfR2 plays a key role in regulating iron homeostasis in the body. GENERAL SIGNIFICANCE The regulation of iron homeostasis is important. One third of the people in the world are anemic. HH is the most common inherited disease in people of Northern European origin and can lead to severe health complications if left untreated. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.
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Antiviral activities in human saliva.
Malamud, D, Abrams, WR, Barber, CA, Weissman, D, Rehtanz, M, Golub, E
Advances in dental research. 2011;(1):34-7
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In this review, the authors survey the large number of antibacterial and antiviral proteins present in human saliva. Of interest, most of these antibacterial proteins display antiviral activity, typically against specific viral pathogens. The review focuses on one protein that interacts with both bacteria and viruses-gp340, originally referred to as salivary agglutinin. In the oral cavity, soluble gp340 binds to and aggregates a variety of bacteria, and this is thought to increase bacterial clearance from the mouth. However, when bound to the tooth surface, gp340 promotes bacterial adherence. In the oral cavity, most gp340 is found soluble in saliva and can function as a specific inhibitor of infectivity of HIV-1 and influenza A. In contrast, in the female reproductive track, most gp340 is bound to the cell surface, where it can promote HIV-1 infection.
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Iron deficiency in critically ill patients: highlighting the role of hepcidin.
Heming, N, Montravers, P, Lasocki, S
Critical care (London, England). 2011;(2):210