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1.
Rational selection of bioactive principles for wound healing applications: Growth factors and antioxidants.
Viaña-Mendieta, P, Sánchez, ML, Benavides, J
International wound journal. 2022;(1):100-113
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Abstract
Wound healing is a complex process of communication between growth factors, reactive species of oxygen, cells, signalling pathways, and cytokines in the extracellular matrix, in which growth factors are the key regulators. In humans, the main regulators of the cellular responses in wound healing are five growth factors, namely EGF, bFGF, VEGF, and TGF-β1. On the other hand, antioxidants such as astaxanthin, beta-carotene, epigallocatechin gallate, delphinidin, and curcumin have been demonstrated to stimulate cell proliferation, migration and angiogenesis, and control inflammation, to suggest a practical approach to design new strategies to treat non-healing cutaneous conditions. Based on the individual effects of growth factors and antioxidants, it may be envisioned that the use of both types of bioactives in wound healing formulations may have an additive or synergistic effect on the healing potential. This review addresses the effect of growth factors and antioxidants on wound healing-related processes. Furthermore, a prospective on their potential additive or synergistic effect on wound healing formulations, based on their individual effects, is presented. This may serve as a guide for the development of a new generation of wound healing formulations.
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2.
Human Milk Growth Factors and Their Role in NEC Prevention: A Narrative Review.
York, DJ, Smazal, AL, Robinson, DT, De Plaen, IG
Nutrients. 2021;(11)
Abstract
Growing evidence demonstrates human milk's protective effect against necrotizing enterocolitis (NEC). Human milk derives these properties from biologically active compounds that influence intestinal growth, barrier function, microvascular development, and immunological maturation. Among these protective compounds are growth factors that are secreted into milk with relatively high concentrations during the early postnatal period, when newborns are most susceptible to NEC. This paper reviews the current knowledge on human milk growth factors and their mechanisms of action relevant to NEC prevention. It will also discuss the stability of these growth factors with human milk pasteurization and their potential for use as supplements to infant formulas with the goal of preventing NEC.
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Human Breast Milk: Bioactive Components, from Stem Cells to Health Outcomes.
Bardanzellu, F, Peroni, DG, Fanos, V
Current nutrition reports. 2020;(1):1-13
Abstract
PURPOSE OF REVIEW Breast milk (BM) is a peculiar fluid owing unique properties and resulting the ideal food during early neonatal period. As widely known, it can improve the outcome of both neonate and lactating mother, influencing their whole life. BM is characterized by several beneficial components; among these, a great role is played by BM own and specific microbiome, deeply investigated in many studies. Moreover, the use of metabolomics in BM analysis allowed a better characterization of its metabolic pathways that vary according to lactation stage and neonatal gestational age. The aim of this review is to describe growth factors, cytokines, immunity mediators, and stem cells (SCs) contained in BM and investigate their functions and effects on neonatal outcome, especially focusing on immuno- and neurodevelopment. RECENT FINDINGS We evaluated recent and updated literature on this field. The article that we analyzed to write this review have been found in MEDLINE using breast milk-derived stem cells, biofactors, growth factors, breastfeeding-related outcomes, neurodevelopment, and neonatal immunological system as keywords. Discovering and characterizing BM components could result very useful to clarify the pathophysiology of their influence on neonatal growth and even to improve artificial formulations' composition. Moreover, since SCs abilities and their involvement in the development of several diseases, they could help to discover specific targets for new therapies. It could be useful to characterize BM-derived SC markers, properties, and variations during lactation stages, to understand their potential role in therapeutic applications, since they could be noninvasively isolated from BM. More studies will help to describe more in detail the characteristics of mother-to-child communication through breastfeeding and its potential role in the next future.
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Human Follicle in vitro Culture Including Activation, Growth, and Maturation: A Review of Research Progress.
Yang, Q, Zhu, L, Jin, L
Frontiers in endocrinology. 2020;:548
Abstract
Fertility preservation has received unprecedented attention nowadays. In addition to cryopreservation and re-implantation of embryos, oocytes, and ovarian tissue pieces, in vitro culture system for follicles/oocytes has been considered as an alternative strategy for fertility preservation. Since the metabolic dynamics and required nutrients are not entirely the same in different stages of follicular development, optimization of each culture step is needed. In this paper, literature regarding culture conditions in three steps were analyzed. Known additives in activation stage included 740Y-P, bpV(HOpic), follicle stimulating hormone (FSH), human serum albumin (HSA), ITS, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and cyclic adenosine monophosphate (cAMP), with different degrees of activation promotion and potential detrimental effect on DNA integrity. For isolated follicles growth stage, actin A, FSH, basic fibroblast growth factor (bFGF), estradiol were proved to improve development or proliferation. As for maturation, addition of growth hormone, melatonin, C-type natriuretic peptide (CNP), GDF9, cilostamide, or forskolin helped to regulate maturation rate or improve oocyte quality. Based on previous sequential culture system for human follicles, optimization is needed to achieve higher maturation rate and better oocyte quality, pursuant to current review, which demonstrated the effects of various additives on different stages.
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Cytokines and Growth Factors as Predictors of Response to Medical Treatment in Diabetic Macular Edema.
Torres-Costa, S, Alves Valente, MC, Falcão-Reis, F, Falcão, M
The Journal of pharmacology and experimental therapeutics. 2020;(3):445-452
Abstract
Diabetic macular edema (DME) is the most common cause of visual loss in patients with diabetes. Antivascular endothelial growth factors (anti-VEGF) agents are first-line therapy for DME. Nevertheless, up to 60% of patients (depending on the anti-VEGF drug used) have an inadequate response to anti-VEGF treatment. Several cytokines are increased in aqueous humor of patients with DME. Differences in response to treatment may be related to baseline cytokine levels. Intravitreal corticosteroids may be used as an alternative to anti-VEGF agents. Steroids have a different pharmacological profile and act on different pathophysiologic mechanisms. Their effect on aqueous humor cytokines is different from the effect of anti-VEGF therapy. This review highlights the major cytokines involved in DME and evaluates whether baseline cytokine levels could be predictors of response to treatment in DME. SIGNIFICANCE STATEMENT Antivascular endothelial growth factor (anti-VEGF) agents are efficient as diabetic macular edema (DME) treatment. However, in some cases, DME fails to respond to anti-VEGF intravitreal injections. Changes in cytokine levels after treatment supported the idea that other cytokines than VEGF are implicated in DME pathogenesis and could be predictors of response to anti-VEGF treatment or corticosteroids allowing targeted and individualized therapy guided by cytokine levels.
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Regulation of plant peptide hormones and growth factors by post-translational modification.
Stührwohldt, N, Schaller, A
Plant biology (Stuttgart, Germany). 2019;:49-63
Abstract
The number, diversity and significance of peptides as regulators of cellular differentiation, growth, development and defence of plants has long been underestimated. Peptides have now emerged as an important class of signals for cell-to-cell communication over short distances, and also for long-range signalling. We refer to these signalling molecules as peptide growth factors and peptide hormones, respectively. As compared to remarkable progress with respect to the mechanisms of peptide perception and signal transduction, the biogenesis of signalling peptides is still in its infancy. This review focuses on the biogenesis and activity of small post-translationally modified peptides. These peptides are derived from inactive pre-pro-peptides of approximately 70-120 amino acids. Multiple post-translational modifications (PTMs) may be required for peptide maturation and activation, including proteolytic processing, tyrosine sulfation, proline hydroxylation and hydroxyproline glycosylation. While many of the enzymes responsible for these modifications have been identified, their impact on peptide activity and signalling is not fully understood. These PTMs may or may not be required for bioactivity, they may inactivate the peptide or modify its signalling specificity, they may affect peptide stability or targeting, or its binding affinity with the receptor. In the present review, we will first introduce the peptides that undergo PTMs and for which these PTMs were shown to be functionally relevant. We will then discuss the different types of PTMs and the impact they have on peptide activity and plant growth and development. We conclude with an outlook on the open questions that need to be addressed in future research.
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The role of new adipokines in gestational diabetes mellitus pathogenesis.
Mierzyński, R, Poniedziałek-Czajkowska, E, Dłuski, D, Leszczyńska-Gorzelak, B
Ginekologia polska. 2018;(4):221-26
Abstract
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition dur-ing pregnancy. Explanation of the GDM pathogenesis is important due to preventing gestational complications. During pregnancy there are significant changes in maternal metabolism. Many of these changes are influenced by different adi-pokines produced in the placenta and adipose tissue. The exact role of adipokines in the pathogenesis of GDM remains still unknown. Several adipokines have been analysed throughout gestation and their levels have been suggested as biomarkers of maternal-perinatal outcomes. Some of them have been postulated as significant in the pathogenesis of pregnancy complications like GDM. This report aims to review some of the recent topics of adipokine research that may be of particular importance in patho-physiology and diagnosis of gestational diabetes mellitus. Because of manuscript length limitations, after thorough literature review and in view of the recent evidence, we focus on the one of the most well-known adipokine: adiponectin, and not so well-studied: nesfatin-1, chemerin, ghrelin, and CTRP 1.
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Implication of a novel Gla-containing protein, Gas6 in the pathogenesis of insulin resistance, impaired glucose homeostasis, and inflammation: A review.
Dihingia, A, Kalita, J, Manna, P
Diabetes research and clinical practice. 2017;:74-82
Abstract
Growth arrest specific 6 (Gas6), a vitamin K-dependent protein plays a significant role in the regulation of cellular homeostasis via binding with TAM-receptor tyrosine kinases. Several studies reported the role of Gas6 in cancer, glomerular injury, obesity, and inflammation, however, very little is known about its role in insulin resistance (IR) and impaired glucose metabolism. Majority of the studies reported an inverse correlation of Gas6 protein levels or gene polymorphism with plasma glucose, HbA1c, IR, and inflammatory cytokines among type 2 diabetes (T2D) and obese subjects. However, few studies reported a positive correlation of Gas6 protein levels or gene polymorphism with IR and inflammation among obese subjects. This review for the first time provides an overview of the association of Gas6 protein levels or gene polymorphism with IR, glucose intolerance, and inflammation among T2D and obese subjects. This review also depicts the probable mechanism underlying the association of Gas6 with glucose intolerance and inflammation. The outcome of this review will increase the understanding about the role of Gas6 in the pathogenesis of IR, glucose intolerance and inflammation and that should in turn lead to the design of clinical interventions to improve glucose metabolism and the lives of the T2D patients.
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Growth factors and beta-tricalcium phosphate in the treatment of periodontal intraosseous defects: A systematic review and meta-analysis of randomised controlled trials.
Cãlin, C, Pãtraşcu, I
Archives of oral biology. 2016;:44-54
Abstract
OBJECTIVE To evaluate the effectiveness at different points in time, of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) coated onto a beta-tricalcium phosphate (β-TCP) carrier compared to β-TCP alone, or to recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a β-TCP scaffold in intraosseous periodontal defects. DESIGN A digital search for randomised controlled trials (RCTs) was conducted on MEDLINE/PubMed. The quality of reporting and the risk of bias of the included RCTs were assessed using the CONSORT guidelines and the Cochrane risk of bias tool. The difference between the means of the outcomes at baseline and at follow-up for each group was tested using the Student's t-test for paired samples. The difference between the means of the outcome changes at follow-up between groups was analysed using the Student's t-test for two independent samples. Prior to each analysis a test of homogeneity of variances (Ansari-Bradley) was performed. RESULTS From 11 articles assessed for eligibility, 5 RCTs were included in this review. The risk of bias was considered to be low in 2 articles, medium in 1 study and high in 2 studies. CONCLUSIONS In the treatment of periodontal intraosseous defects the application of rhPDGF-BB/β-TCP improved all outcomes when compared to β-TCP at 6 months follow-up. Either rhPDGF-BB/β-TCP or rhGDF-5/β-TCP seemed to provide similar results in terms of probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain. The application of rhGDF-5/β-TCP resulted in a more pronounced reduction in gingival recession (GR) depth at 6 months follow-up compared to rhPDGF-BB/β-TCP.
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10.
Jagged1 (JAG1): Structure, expression, and disease associations.
Grochowski, CM, Loomes, KM, Spinner, NB
Gene. 2016;(1 Pt 3):381-4
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Abstract
Jagged1 (JAG1) is one of the 5 cell surface ligands that functions primarily in the highly conserved Notch signaling pathway. Notch signaling plays a critical role in cellular fate determination and is active throughout development and across many organ systems. The classic JAG1-NOTCH interaction leads to a cascade of proteolytic cleavages resulting in the NOTCH intracellular domain being transported into the nucleus where it functions to activate downstream transcription of target genes. JAG1 mutations have been associated with several disorders including the multi-system dominant disorder Alagille syndrome, and some cases of tetralogy of Fallot (although these may represent variable expressivity of Alagille syndrome). In addition, variations in JAG1 have been found to be associated with multiple types of cancer including breast cancer and adrenocortical carcinoma. Alagille syndrome, which primarily affects the liver, heart, skeleton, eye, face, kidney and vasculature is caused by loss of function mutations in JAG1, demonstrating that haploinsufficiency for JAG1 is disease causing, at least in these tissues. Expression and conditional gene knockout studies of JAG1 (Jag1) have correlated with tissue-specific disease phenotypes and have provided insight into both disease pathogenesis and human development.