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1.
The structural reconformation of peptides in enhancing functional and therapeutic properties: Insights into their solid state crystallizations.
Saadi, S, Ghazali, HM, Saari, N, Abdulkarim, SM
Biophysical chemistry. 2021;:106565
Abstract
Therapeutic peptides derived proteins with alpha-reconformation states like antibody shape have shown potential effects in combating terrible diseases linked with earlier signs of angiogensis, mutagenesis and transgenesis. Alpha reconformation in material design refers to the folding of the peptide chains and their transitions under reversible chemical bonds of disulfide chemical bridges and further non-covalence lesions. Thus, the rational design of signal peptides into alpha-helix is intended in increasing the defending effects of peptides into cores like adjuvant antibiotic and/or vaccines. Thereby, the signal peptides are able in displaying multiple eradicating regions by changing crystal-depositions and deviation angles. These types of molecular structures could have multiple advantages in tracing disease syndromes and impurities by increasing the host defense against the fates of pathogens and viruses, eventually leading to the loss in signaling by increasing peptide susceptibility levels to folding and unfolding and therefore, formation of transgenic peptide models. Alpha reconformation peptides is aimed in triggering as well as other regulatory functions such as remodulating metabolic chain disorders of lipolysis and glucolysis by increasing the insulin and leptin resistance for best lipid storages and lipoprotein density distributions.
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2.
The new place of enterohormones in intestinal failure.
Daoud, DC, Joly, F
Current opinion in clinical nutrition and metabolic care. 2020;(5):344-349
Abstract
PURPOSE OF REVIEW Since the approval of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, for the treatment of patients with short bowel syndrome (SBS) associated with intestinal failure, enterohormone therapy has received significant interest and is becoming the first choice of treatment in selected patients. As such, it is paramount to assess and understand the new place of hormonal therapy in the algorithm of treatments in SBS-intestinal failure. RECENT FINDINGS Specialized intestinal failure units have recently reported their outcomes with teduglutide to evaluate if they are consistent with the phase III trials results. SBS-intestinal failure patients are very heterogenous including their response to this treatment, hence the importance of real-life studies beyond the context of clinical trials. Moreover, it is essential to find a consensus on criteria identifying candidate patients for teduglutide. In addition, the impact of teduglutide on quality of life and its cost-effectiveness are emerging as well as new enterohormone treatments are being studied whether it is long action GLP-2 analog or other ileocolonic break hormones like glucagon-like peptide-1 analog. SUMMARY Hormonotherapy is currently modifying the natural history of patients with SBS-intestinal failure by decreasing their need for parenteral support and possibly even complications associated with long-term parenteral support. Enterohormone treatment is now the cornerstone in SBS-intestinal failure and should be offered as a first-line therapy to selected patients.
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3.
Neurotransmitter, neuropeptide and gut peptide profile in PCOS-pathways contributing to the pathophysiology, food intake and psychiatric manifestations of PCOS.
Ilie, IR
Advances in clinical chemistry. 2020;:85-135
Abstract
Polycystic ovary syndrome (PCOS) is a major health problem with a heterogeneous hormone-imbalance and clinical presentation across the lifespan of women. Increased androgen production and abnormal gonadotropin-releasing hormone (GnRH) release and gonadotropin secretion, resulting in chronic anovulation are well-known features of the PCOS. The brain is both at the top of the neuroendocrine axis regulating ovarian function and a sensitive target of peripheral gonadal hormones and peptides. Current literature illustrates that neurotransmitters regulate various functions of the body, including reproduction, mood and body weight. Neurotransmitter alteration could be one of the reasons for disturbed GnRH release, consequently directing the ovarian dysfunction in PCOS, since there is plenty evidence for altered catecholamine metabolism and brain serotonin or opioid activity described in PCOS. Further, the dysregulated neurotransmitter and neuropeptide profile in PCOS could also be the reason for low self-esteem, anxiety, mood swings and depression or obesity, features closely associated with PCOS women. Can these altered central brain circuits, or the disrupted gut-brain axis be the tie that would both explain and link the pathogenesis of this disorder, the occurrence of depression, anxiety and other mood disorders as well as of obesity, insulin resistance and abnormal appetite in PCOS? This review intends to provide the reader with a comprehensive overview of what is known about the relatively understudied, but very complex role that neurotransmitters, neuropeptides and gut peptides play in PCOS. The answer to the above question may help the development of drugs to specifically target these central and peripheral circuits, thereby providing a valuable treatment for PCOS patients that present to the clinic with GnRH/LH hypersecretion, obesity or psychiatric manifestations.
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4.
Current state of art after twenty years of the discovery of bioactive peptide lunasin.
Fernández-Tomé, S, Hernández-Ledesma, B
Food research international (Ottawa, Ont.). 2019;:71-78
Abstract
Non-communicable diseases have become the medical challenge of the 21st century because of their high incidence and mortality rates. Accumulating evidence has suggested that the modulation of diet and other lifestyle habits is the best strategy for the prevention of these diseases. An increasing number of dietary compounds have been found to exert health promoting benefits beyond their nutritional effects. Among them, lunasin is considered one of the most studied bioactive peptides. Since its discovery in soybean twenty years ago, many researchers around the world have focused their studies on demonstrating the chemopreventive and chemotherapeutic activity of lunasin. Moreover, in the last years, promising protective effects of this peptide against hypercholesterolemia, obesity, metabolic syndrome and associated cardiovascular disorders, and inflammatory and immune-regulated diseases have been described. This review summarizes recent remarkable advances on the use of peptide lunasin as a potential functional ingredient to provide health benefits. Moreover, novel aspects related to the influence of lunasin's digestion and bioavailability, the mechanisms of action proposed to explain the underlying biological properties, and the incorporation of this peptide into nutritional supplements are critically discussed.
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5.
New peptides players in metabolic disorders.
Mierzwicka, A, Bolanowski, M
Postepy higieny i medycyny doswiadczalnej (Online). 2016;(0):881-6
Abstract
Among new peptides responsible for the pathogenesis of metabolic disorders and carbohydrate metabolism, adipokines are of great importance. Adipokines are substances of hormonal character, secreted by adipose tissue. Apart from the well-known adipokines, adropin and preptin are relatively newly discovered, hence their function is not fully understood. They are peptides not secreted by adipose tissue but their role in the metabolic regulations seems to be significant. Preptin is a 34-amino acid peptide, a derivative of proinsulin growth factor II (pro-IGF-II), secreted by pancreatic β cells, considered to be a physiological enhancer of insulin secretion. Additionally, preptin has a stimulating effect on osteoblasts, inducing their proliferation, differentiation and survival. Adropin is a 76-amino acid peptide, encoded by the energy homeostasis associated gene (Enho), mainly in liver and brain, and its expression is dependent on a diet. Adropin is believed to play an important role in metabolic homeostasis, fatty acids metabolism control, insulin resistance prevention, dyslipidemia, and impaired glucose tolerance. The results of studies conducted so far show that the diseases resulting from metabolic syndrome, such as obesity, type 2 diabetes mellitus, polycystic ovary syndrome, non-alcoholic fatty liver disease, or cardiovascular disease are accompanied by significant changes in the concentration of these peptides. It is also important to note that preptin has an anabolic effect on bone tissue, which might be preventive in osteoporosis.
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6.
Gut hormones in the treatment of short-bowel syndrome and intestinal failure.
Jeppesen, PB
Current opinion in endocrinology, diabetes, and obesity. 2015;(1):14-20
Abstract
PURPOSE OF REVIEW The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 teduglutide studies, and pilot studies employing GLP-1 and agonists for this orphan condition. RECENT FINDINGS In a 3-week, phase 2, metabolic balance study, teduglutide increased the intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 Kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Adverse events were mainly of gastrointestinal origin and consistent with the known mechanism of action of teduglutide. Pilot studies suggest that GLP-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2. SUMMARY Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation in these severely disabled short-bowel syndrome patients.
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7.
New approaches to the treatments of short bowel syndrome-associated intestinal failure.
Jeppesen, PB
Current opinion in gastroenterology. 2014;(2):182-8
Abstract
PURPOSE OF REVIEW Teduglutide, a recombinant analog of human glucagon-like peptide 2, has recently been approved in the US and Europe (Gattex and Revestive, respectively) as the first targeted treatment of short bowel syndrome-associated intestinal failure (SBS-IF). Glucagon-like peptide 2 improves structural and functional intestinal adaptation following intestinal resection by decelerating a rapid gastric emptying, by decreasing gastric hypersecretion, by increasing intestinal blood flow and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 studies preceding the US Food and Drug Administration and the European Medicines Agency approval of subcutaneous teduglutide for this orphan condition. RECENT FINDINGS In a 3-week, phase 2, metabolic balance study, teduglutide increased intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Teduglutide had an acceptable tolerability profile, where adverse events generally were of gastrointestinal origin consistent with the known mechanism of action. SUMMARY Teduglutide will add incremental benefit to the limited medical treatment armamentarium in SBS patients by maximizing intestinal absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. Future research should target and implement other key hormones with similar and possible additive or synergistic effects, thereby further promoting structural and functional adaptation and intestinal rehabilitation in these severely disabled SBS patients.
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8.
Modern treatment of short bowel syndrome.
Jeppesen, PB
Current opinion in clinical nutrition and metabolic care. 2013;(5):582-7
Abstract
PURPOSE OF REVIEW Recently, the US Food and Drug Administration and the European Medicines Agency approved the glucagon-like peptide 2 analogue, teduglutide, for the treatment of short bowel syndrome (SBS), and this review describes the physiological basis for its clinical use. RECENT FINDINGS By affecting the intestinal neuroendocrine system, hormones may promote the growth of the intestinal mucosa, restore a more normal gastric emptying and secretion, stimulate intestinal blood flow, increase intestinal barrier function, immunity and absorption, and thereby promote structural and functional adaptation following intestinal resection. In a 3-week, phase 2, metabolic balance study, teduglutide increased intestinal wet weight absorption by ∼700 g/day and reduced faecal energy losses by ∼0.8 MJ/day. In two subsequent 24-week, phase 3 studies in SBS patients with intestinal failure (SBS-IF), teduglutide reduced the need for parenteral support in the same magnitude. SUMMARY Teduglutide adds incremental benefit to the limited medical treatment armamentarium in SBS patients. Modern treatments should aim to maximize remnant intestinal absorption, decrease malabsorption and accompanying symptoms, reduce the need, burdens and complications related to parenteral support, and ultimately improve the health-related quality of life in SBS-IF patients. Future research should target and implement other key hormones with similar effects, thereby promoting intestinal adaptation and rehabilitation in SBS patients.
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9.
Treatment of adult short bowel syndrome patients with teduglutide.
Nørholk, LM, Holst, JJ, Jeppesen, PB
Expert opinion on pharmacotherapy. 2012;(2):235-43
Abstract
INTRODUCTION Parenteral support is lifesaving in short bowel syndrome patients with intestinal failure (SBS-IF), who are unable to compensate for their malabsorption by metabolic or pharmacologic adaptation. Mutually, the symptoms of SBS-IF and the inconveniences and complications in relation to parenteral support may cause impairment of the quality of life of SBS-IF patients. Conventional treatments include dietary manipulations, oral rehydration solutions, antidiarrheal and antisecretory treatments. However, the evidence base for these interventions is limited, and treatments improving structural and functional integrity of the remaining intestine are desired. Teduglutide , an analog of glucagon-like peptide 2, improves intestinal rehabilitation by promoting mucosal growth and possibly by inhibiting gastric emptying and secretion, which in turn reduces intestinal losses and promotes intestinal absorption. AREAS COVERED This paper reviews the following findings: in a 3-week, Phase II balance study, teduglutide reduced diarrhea by ∼ 700 g/day and fecal energy losses by ∼ 0.8 MJ/day, and in a randomized, placebo-controlled, 24-week, Phase III study, corresponding reductions in the need for parenteral support were obtained. EXPERT OPINION Teduglutide seems to be safe and well-tolerated and demonstrates restoration of structural and functional integrity of the remaining intestine with significant intestinotrophic and proabsorptive effects, facilitating a reduction in diarrhea and an equivalent reduction in the need for parenteral support in SBS-IF patients.
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10.
A carbohydrate-restricted diet alters gut peptides and adiposity signals in men and women with metabolic syndrome.
Hayes, MR, Miller, CK, Ulbrecht, JS, Mauger, JL, Parker-Klees, L, Gutschall, MD, Mitchell, DC, Smiciklas-Wright, H, Covasa, M
The Journal of nutrition. 2007;(8):1944-50
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Abstract
Carbohydrate-restricted diets have been shown to enhance satiation- and other homeostatic-signaling pathways controlling food intake and energy balance, which may serve to reduce the incidence of obesity and metabolic syndrome. This study was designed as a correlational, observational investigation of the effects of a carbohydrate-restricted diet on weight loss and body fat reduction and associated changes in circulating leptin, insulin, ghrelin, and cholecystokinin (CCK) concentrations in overweight/obese patients (4 men and 16 women) with metabolic syndrome. Subjects received clinical instruction on the initiation and maintenance of the commercial South Beach Diet, consisting of 2 phases: Phase I (initial 2 wk of the study) and Phase II (remaining 10 wk). Participants showed a decrease (P < 0.05) in body weight (93.5 +/- 3.6 kg vs. 88.3 +/- 3.4 kg), BMI (33.9 +/- 1.3 kg/m(2) vs. 32.0 +/- 1.3 kg/m(2)), waist circumference (112.8 +/- 2.8 cm vs. 107.7 +/- 3.0 cm), and total percent body fat (40.2 +/- 1.5% vs. 39.2 +/- 1.5%) by study completion. Plasma fasting insulin and leptin concentrations decreased significantly from baseline concentrations (139.1 +/- 12.2 pmol/L and 44.1 +/- 4.5 microg/L, respectively) by the end of Phase I (98.6 +/- 2.6 pmol/L and 33.3 +/- 4.1 microg/L, respectively). Plasma fasting ghrelin concentrations significantly increased from baseline (836.7 +/- 66.7 ng/L) by Phase II (939.9 +/- 56.8 ng/L). The postprandial increase in plasma CCK concentrations (difference in plasma CCK concentrations from fasting to postprandial) after Phase I (2.4 +/- 0.3 pmol/L) and Phase II (2.5 +/- 0.4 pmol/L) was significantly greater than the postprandial increase at baseline (1.1 +/- 0.5 pmol/L). Collectively, these results suggest that in patients with metabolic syndrome, improved adiposity signaling and increased postprandial CCK concentrations may act together as a possible compensatory control mechanism to maintain low intakes and facilitate weight loss, despite an increase in fasting ghrelin concentrations and subjective measures of hunger.