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1.
Role of Glutathionylation in Infection and Inflammation.
Checconi, P, Limongi, D, Baldelli, S, Ciriolo, MR, Nencioni, L, Palamara, AT
Nutrients. 2019;(8)
Abstract
Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by different cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses.
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2.
Managing Risks with Biologics.
Click, B, Regueiro, M
Current gastroenterology reports. 2019;(2):1
Abstract
PURPOSE OF REVIEW With a rapidly evolving complement of advanced targeted therapies in inflammatory bowel disease, additional safety and side effect concerns emerge. It is the purpose of this review to consider various risks with biologic therapies in inflammatory bowel disease and discuss mitigating strategies. RECENT FINDINGS Two recently approved monoclonal antibodies (vedolizumab and ustekinumab) and a Janus kinase inhibitor small molecule (tofacitnib) have introduced a number of novel safety and risk considerations. We review the clinical trial and real-world safety data to date on these agents as well as review new data and considerations with anti-tumor necrosis factor agents. New vaccines for varicella zoster virus, hepatitis B virus, and high-dose influenza have been studied, and we discuss the clinical importance of these findings. Lastly, we make management recommendations in the event of particular side effects or complications. Understanding the risks of new agents in inflammatory bowel disease, potential mitigating strategies, and management considerations is important to achieving and maintaining clinical outcomes in IBD patients.
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3.
Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings.
Mukherjee, S, Joardar, N, Sengupta, S, Sinha Babu, SP
The Journal of nutritional biochemistry. 2018;:111-128
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Abstract
The human gut microbiota has been the interest of extensive research in recent years and our knowledge on using the potential capacity of these microbes are growing rapidly. Microorganisms colonized throughout the gastrointestinal tract of human are coevolved through symbiotic relationship and can influence physiology, metabolism, nutrition and immune functions of an individual. The gut microbes are directly involved in conferring protection against pathogen colonization by inducing direct killing, competing with nutrients and enhancing the response of the gut-associated immune repertoire. Damage in the microbiome (dysbiosis) is linked with several life-threatening outcomes viz. inflammatory bowel disease, cancer, obesity, allergy, and auto-immune disorders. Therefore, the manipulation of human gut microbiota came out as a potential choice for therapeutic intervention of the several human diseases. Herein, we review significant studies emphasizing the influence of the gut microbiota on the regulation of host responses in combating infectious and inflammatory diseases alongside describing the promises of gut microbes as future therapeutics.
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4.
Syzygium Cordatum Hochst. ex Krauss: An Overview of Its Ethnobotany, Phytochemistry and Pharmacological Properties.
Maroyi, A
Molecules (Basel, Switzerland). 2018;(5)
Abstract
Syzygium cordatum is a valuable medicinal plant in the materia medica of east and southern Africa. The aim of this study was to review the botany, medicinal uses, phytochemistry and ethnopharmacological properties of S. cordatum. Relevant literature search was carried out using internet sources such as ACS, Web of Science, Wiley, SpringerLink, Scopus, Mendeley, Google Scholar, Pubmed, SciFinder, BioMed Central, Science Direct and Elsevier. Other literature sources were conference papers, book chapters, books, theses and websites. The leaves, roots, bark and fruits of S. cordatum are used as ethnomedicines against 24 human diseases such as gastro-intestinal disorders, burns, sores, wounds, colds, cough, respiratory complaints, sexually transmitted infections (STIs), tuberculosis, fever and malaria. Several phytochemical compounds including alkaloids, anthocyanidin, essential oils, flavonoids, leucoanthocyanidin, phenols, phytosterols, saponins, simple sugars, terpenoids and triterpenoid have been identified from S. cordatum. Pharmacological evaluations revealed that S. cordatum is characterized by several biological activities including antibacterial, antifungal, antidiarrheal, anti-sexually transmitted infections, antidiabetic, anticholinesterase, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial and anti-proteus. These pharmacological findings lend credence to the traditional ethnomedicinal uses and ethnopharmacological importance of S. cordatum. Future research on the species should identify the biological compounds, their mode of action and physiological pathways and clinical relevance.
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5.
Cdc42 - A tryst between host cholesterol metabolism and infection.
Sviridov, D, Mukhamedova, N
Small GTPases. 2018;(3):237-241
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Abstract
Emerging evidence points to an important connection between pathogenesis of intracellular infections and host cholesterol metabolism. In our study we demonstrated that human cytomegalovirus exploits host small GTPase Cdc42 to hijack cellular cholesterol efflux pathway. It appears that the virus uses host machinery to stimulate cholesterol efflux by modifying lipid rafts and altering properties of plasma membrane, but the altered pathway is controlled by the viral protein US28 instead of the host ATP binding cassette transporter A1. We speculate that virus-controlled remodeling of plasma membrane facilitates immune evasion, exocytosis of viral proteins and cell-to-cell transmission of human cytomegalovirus. These mechanisms may be not unique for the cytomegalovirus and subverting reverse cholesterol transport pathway may be a generic mechanism used by pathogens to alter properties of host plasma membrane adapting it for their purposes-to hide and disseminate.
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Intrauterine infection, immune system and premature birth.
Helmo, FR, Alves, EAR, Moreira, RAA, Severino, VO, Rocha, LP, Monteiro, MLGDR, Reis, MAD, Etchebehere, RM, Machado, JR, Corrêa, RRM
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(9):1227-1233
Abstract
Preterm birth accounts for nearly one million deaths among children under five years of age, and although its etiopathogenesis is not fully elucidated, ascending intrauterine infection and fetal inflammatory response seem to be the main triggers. The intense inflammatory response mediated by IL-1β, TNF-α, PAF, IFN-γ and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage and rupture, increased uterine contractions and biochemical and structural changes in the cervix. Furthermore, preterm neonates have deficient innate and adaptive immune responses characterized by reduced levels of IgG, opsonization and phagocytosis, as well as increased activation of Th1 cells in relation to Th2 cells. Therefore, this triad is favors the occurrence of neonatal complications, such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Due to serious maternal and child health complications of intrauterine infection, several studies have tried to identify biomarkers for the early diagnosis of this entity. This literature review aims to discuss the main scientific findings regarding the association between ascending intrauterine infection, immune system and preterm birth.
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Infections: A Possible Risk Factor for Type 2 Diabetes.
Chakraborty, S, Bhattacharyya, R, Banerjee, D
Advances in clinical chemistry. 2017;:227-251
Abstract
Diabetes mellitus is one of the biggest challenges to human health globally, with an estimated 95% of the global diabetic population having type 2 diabetes. Classical causes for type 2 diabetes, such as genetics and obesity, do not account for the high incidence of the disease. Recent data suggest that infections may precipitate insulin resistance via multiple mechanisms, such as the proinflammatory cytokine response, the acute-phase response, and the alteration of the nutrient status. Even pathogen products, such as lipopolysaccharide and peptidoglycans, can be diabetogenic. Therefore, we argue that infections that are known to contribute to insulin resistance should be considered as risk factors for type 2 diabetes.
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The Metabolic Response to Stress and Infection in Critically Ill Children: The Opportunity of an Individualized Approach.
De Cosmi, V, Milani, GP, Mazzocchi, A, D'Oria, V, Silano, M, Calderini, E, Agostoni, C
Nutrients. 2017;(9)
Abstract
The metabolic response to stress and infection is closely related to the corresponding requirements of energy and nutrients. On a general level, the response is driven by a complex endocrine network and related to the nature and severity of the insult. On an individual level, the effects of nutritional interventions are highly variable and a possible source of complications. This narrative review aims to discuss the metabolic changes in critically-ill children and the potential of developing personalized nutritional interventions. Through a literature search strategy, we have investigated the importance of blood glucose levels, the nutritional aspects of the different phases of acute stress response, and the reliability of the available tools to assess the energy expenditure. The dynamics of metabolism during stressful events reveals the difficult balance between risk of hypo- or hyperglycemia and under- or overfeeding. Within this context, individualized and accurate measurement of energy expenditure may help in defining the metabolic needs of patients. Given the variability of the metabolic response in critical conditions, randomized clinical studies in ill children are needed to evaluate the effect of individualized nutritional intervention on health outcomes.
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Plants and other natural products used in the management of oral infections and improvement of oral health.
Chinsembu, KC
Acta tropica. 2016;:6-18
Abstract
Challenges of resistance to synthetic antimicrobials have opened new vistas in the search for natural products. This article rigorously reviews plants and other natural products used in oral health: Punica granatum L. (pomegranate), Matricaria recutita L. (chamomile), Camellia sinensis (L.) Kuntze (green tea), chewing sticks made from Diospyros mespiliformis Hochst. ex A.D.C., Diospyros lycioides Desf., and Salvadora persica L. (miswak), honey and propolis from the manuka tree (Leptospermum scoparium J.R. Forst. & G. Forst.), rhein from Rheum rhabarbarum L. (rhubarb), dried fruits of Vitis vinifera L. (raisins), essential oils, probiotics and mushrooms. Further, the review highlights plants from Africa, Asia, Brazil, Mexico, Europe, and the Middle East. Some of the plants' antimicrobial properties and chemical principles have been elucidated. While the use of natural products for oral health is prominent in resource-poor settings, antimicrobial testing is mainly conducted in the following countries (in decreasing order of magnitude): India, South Africa, Brazil, Japan, France, Egypt, Iran, Mexico, Kenya, Switzerland, Nigeria, Australia, Uganda, and the United Kingdom. While the review exposes a dire gap for more studies on clinical efficacy and toxicity, the following emerging trend was noted: basic research on plants for oral health is mainly done in Brazil, Europe and Australia. Brazil, China, India and New Zealand generally conduct value addition of natural products for fortification of toothpastes. African countries focus on bioprospecting and primary production of raw plants and other natural products with antimicrobial efficacies. The Middle East and Egypt predominantly research on plants used as chewing sticks. More research and funding are needed in the field of natural products for oral health, especially in Africa where oral diseases are fuelled by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
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10.
Iron Localization and Infectious Disease in Chronic Kidney Disease Patients.
Nakanishi, T, Kuragano, T, Nanami, M, Hasuike, Y
American journal of nephrology. 2016;(4):237-44
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Abstract
For patients on dialysis, infection is the second leading cause of mortality. Iron metabolism should be considered in the pathogenesis of infectious disease, as high local iron concentrations favor the growth of many microbes. This review is intended to provide information regarding iron metabolism and infection in chronic kidney disease (CKD) patients. There are 2 reasons these patients may be vulnerable to infection: (1) the excessive iron administered to treat renal anemia could be associated with impairments of the host's innate immune response, (2) CKD-associated inflammation could cause dysregulated iron metabolism. Pathogenic microorganisms can be categorized as extracellular or intracellular pathogens. The proliferation site may determine the degree of virulence. In cases of mainly extracellular microbial growth, the host's strategy of sequestering iron in cells may efficiently inhibit proliferation. However, the same strategy may favor the intracellular growth of microorganisms. The administration of excessive amounts of iron may modify iron localization by an increase in the hepcidin concentration. We conclude that there is a need for large multicenter randomized controlled trials to evaluate the long-term safety of different iron administration patterns that allow for a lower infection rate while still producing efficient erythropoiesis in CKD patients.