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1.
Backstage of Eating Disorder-About the Biological Mechanisms behind the Symptoms of Anorexia Nervosa.
Skowron, K, Kurnik-Łucka, M, Dadański, E, Bętkowska-Korpała, B, Gil, K
Nutrients. 2020;(9)
Abstract
Anorexia nervosa (AN) represents a disorder with the highest mortality rate among all psychiatric diseases, yet our understanding of its pathophysiological components continues to be fragmentary. This article reviews the current concepts regarding AN pathomechanisms that focus on the main biological aspects involving central and peripheral neurohormonal pathways, endocrine function, as well as the microbiome-gut-brain axis. It emerged from the unique complexity of constantly accumulating new discoveries, which hamper the ability to look at the disease in a more comprehensive way. The emphasis is placed on the mechanisms underlying the main symptoms and potential new directions that require further investigation in clinical settings.
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Biochemical basis for the regulation of biosynthesis of antiparasitics by bacterial hormones.
Kapoor, I, Olivares, P, Nair, SK
eLife. 2020
Abstract
Diffusible small molecule microbial hormones drastically alter the expression profiles of antibiotics and other drugs in actinobacteria. For example, avenolide (a butenolide) regulates the production of avermectin, derivatives of which are used in the treatment of river blindness and other parasitic diseases. Butenolides and γ-butyrolactones control the production of pharmaceutically important secondary metabolites by binding to TetR family transcriptional repressors. Here, we describe a concise, 22-step synthetic strategy for the production of avenolide. We present crystal structures of the butenolide receptor AvaR1 in isolation and in complex with avenolide, as well as those of AvaR1 bound to an oligonucleotide derived from its operator. Biochemical studies guided by the co-crystal structures enable the identification of 90 new actinobacteria that may be regulated by butenolides, two of which are experimentally verified. These studies provide a foundation for understanding the regulation of microbial secondary metabolite production, which may be exploited for the discovery and production of novel medicines.
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3.
Interplay between Hormones and Several Abiotic Stress Conditions on Arabidopsis thaliana Primary Root Development.
López-Ruiz, BA, Zluhan-Martínez, E, Sánchez, MP, Álvarez-Buylla, ER, Garay-Arroyo, A
Cells. 2020;(12)
Abstract
As sessile organisms, plants must adjust their growth to withstand several environmental conditions. The root is a crucial organ for plant survival as it is responsible for water and nutrient acquisition from the soil and has high phenotypic plasticity in response to a lack or excess of them. How plants sense and transduce their external conditions to achieve development, is still a matter of investigation and hormones play fundamental roles. Hormones are small molecules essential for plant growth and their function is modulated in response to stress environmental conditions and internal cues to adjust plant development. This review was motivated by the need to explore how Arabidopsis thaliana primary root differentially sense and transduce external conditions to modify its development and how hormone-mediated pathways contribute to achieve it. To accomplish this, we discuss available data of primary root growth phenotype under several hormone loss or gain of function mutants or exogenous application of compounds that affect hormone concentration in several abiotic stress conditions. This review shows how different hormones could promote or inhibit primary root development in A. thaliana depending on their growth in several environmental conditions. Interestingly, the only hormone that always acts as a promoter of primary root development is gibberellins.
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Differences in circulating appetite-related hormone concentrations between younger and older adults: a systematic review and meta-analysis.
Johnson, KO, Shannon, OM, Matu, J, Holliday, A, Ispoglou, T, Deighton, K
Aging clinical and experimental research. 2020;(7):1233-1244
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Abstract
Ageing is associated with reduced appetite and energy intakes. However, the mechanisms underlying this phenomenon are not fully understood. This systematic review and meta-analysis quantified differences in circulating concentrations of appetite-related hormones between healthy older and younger adults. Six databases were searched through 12th June 2018 for studies that compared appetite-related hormone concentrations between older and younger adults. Data were pooled using random-effects meta-analysis and are presented as standardised mean difference (Hedges' g) with 95% confidence intervals (95% CI). Thirty-five studies were included involving 710 older adults (mean ± SD; age: 73 ± 5 years) and 713 younger adults (age: 28 ± 7 years). Compared with younger adults, older adults exhibited higher fasted and postprandial concentrations of the anorectic hormones cholecystokinin (Fasted: SMD 0.41 (95% CI 0.24, 0.57); p < 0.001. Postprandial: SMD 0.41 (0.20, 0.62); p < 0.001), leptin [Fasted: SMD 1.23 (0.15, 2.30); p = 0.025. Postprandial: SMD 0.62 (0.23, 1.01); p = 0.002] and insulin [Fasted: SMD 0.24 (- 0.02, 0.50); p = 0.073. Postprandial: SMD 0.16 (0.01, 0.32); p = 0.043]. Higher postprandial concentrations of peptide-YY were also observed in older adults compared with younger adults [SMD 0.31 (- 0.03, 0.65); p = 0.075]. Compared with younger adults, older adults had lower energy intakes [SMD - 0.98 (- 1.74, - 0.22); p = 0.011], and lower hunger perceptions in the fasted [SMD - 1.00 (- 1.54, - 0.46); p < 0.001] and postprandial states [SMD - 0.31, (- 0.64, 0.02); p = 0.064]. Higher circulating concentrations of insulin, leptin, cholecystokinin and peptide-YY accord with reduced appetite and energy intakes in healthy older adults. Interventions to reduce circulating levels of these hormones may be beneficial for combatting the anorexia of ageing.
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How Hormones and MADS-Box Transcription Factors Are Involved in Controlling Fruit Set and Parthenocarpy in Tomato.
Molesini, B, Dusi, V, Pennisi, F, Pandolfini, T
Genes. 2020;(12)
Abstract
Fruit set is the earliest phase of fruit growth and represents the onset of ovary growth after successful fertilization. In parthenocarpy, fruit formation is less affected by environmental factors because it occurs in the absence of pollination and fertilization, making parthenocarpy a highly desired agronomic trait. Elucidating the genetic program controlling parthenocarpy, and more generally fruit set, may have important implications in agriculture, considering the need for crops to be adaptable to climate changes. Several phytohormones play an important role in the transition from flower to fruit. Further complexity emerges from functional analysis of floral homeotic genes. Some homeotic MADS-box genes are implicated in fruit growth and development, displaying an expression pattern commonly observed for ovary growth repressors. Here, we provide an overview of recent discoveries on the molecular regulatory gene network underlying fruit set in tomato, the model organism for fleshy fruit development due to the many genetic and genomic resources available. We describe how the genetic modification of components of this network can cause parthenocarpy, discussing the contribution of hormonal signals and MADS-box transcription factors.
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In Search of New Therapeutics-Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond.
Wawrzkiewicz-Jałowiecka, A, Kowalczyk, K, Trybek, P, Jarosz, T, Radosz, P, Setlak, M, Madej, P
International journal of molecular sciences. 2020;(19)
Abstract
In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17α-hydroxylase), 3β-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.
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Placental Regulation of Energy Homeostasis During Human Pregnancy.
Armistead, B, Johnson, E, VanderKamp, R, Kula-Eversole, E, Kadam, L, Drewlo, S, Kohan-Ghadr, HR
Endocrinology. 2020;(7)
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Abstract
Successful pregnancies rely on sufficient energy and nutrient supply, which require the mother to metabolically adapt to support fetal needs. The placenta has a critical role in this process, as this specialized organ produces hormones and peptides that regulate fetal and maternal metabolism. The ability for the mother to metabolically adapt to support the fetus depends on maternal prepregnancy health. Two-thirds of pregnancies in the United States involve obese or overweight women at the time of conception. This poses significant risks for the infant and mother by disrupting metabolic changes that would normally occur during pregnancy. Despite well characterized functions of placental hormones, there is scarce knowledge surrounding placental endocrine regulation of maternal metabolic trends in pathological pregnancies. In this review, we discuss current efforts to close this gap of knowledge and highlight areas where more research is needed. As the intrauterine environment predetermines the health and wellbeing of the offspring in later life, adequate metabolic control is essential for a successful pregnancy outcome. Understanding how placental hormones contribute to aberrant metabolic adaptations in pathological pregnancies may unveil disease mechanisms and provide methods for better identification and treatment. Studies discussed in this review were identified through PubMed searches between the years of 1966 to the present. We investigated studies of normal pregnancy and metabolic disorders in pregnancy that focused on energy requirements during pregnancy, endocrine regulation of glucose metabolism and insulin resistance, cholesterol and lipid metabolism, and placental hormone regulation.
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Endocrinology and immunology of acne: Two sides of the same coin.
Zouboulis, CC
Experimental dermatology. 2020;(9):840-859
Abstract
Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.
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The effect of probiotics, prebiotics, and synbiotics on hormonal and inflammatory indices in women with polycystic ovary syndrome: a systematic review and meta-analysis.
Shamasbi, SG, Ghanbari-Homayi, S, Mirghafourvand, M
European journal of nutrition. 2020;(2):433-450
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is among the most prevalent endocrine disorders in women and can lead to many other disorders and chronic diseases. Thus, early diagnosis and treatment of this syndrome is important. Using probiotics, prebiotics, and synbiotics supplementations to treat PCOS seems appropriate because of their useful effects and low complications. AIMS To assess the effects of probiotics, prebiotics, and synbiotics on hormonal indices such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin, Free Androgen Index (FAI), and inflammatory indices, such as high sensitive C reactive protein (hsCRP), malondialdehyde (MDA), total glutathione (GSH), nitric oxide (NO), and total antioxidant capacity (TAC) as the primary outcomes and the hirsutism score as the secondary outcome. METHODS All published articles from the beginning until 10 November 2018 in English (Cochrane Library, Web of Sciences, Google Scholar, PubMed, Scopus, and ProQuest) and Persian (SID and Magiran) databases were searched. The effect of interventions on the outcomes was reported with a standard mean difference (SMD) and confidence interval of 95%. In case of high heterogeneity, the random effect model was used instead of the fixed effect model. The statistical heterogeneity of the included clinical trials was tested using the Chi square test and I2. RESULTS Thirteen studies with 855 participants with PCOS(438 women in the intervention group and 417 women in the control group) were included in the meta-analysis. Results of the meta-analysis showed that the SHBG (SMD: 0.56; 95% CI 0.26-0.86; P = 0.0002) and NO (SMD: 0.38; 95% CI 0.09-0.68; P = 0.01) concentration increased significantly in the probiotics and synbiotics groups compared to the placebo group. FAI (SMD: - 0.58; 95% CI - 0.95 to - 0.21; P = 0.002) and MDA (SMD: - 0.76; 95% CI - 1.46 to - 0.05; P = 0.03) concentration in the probiotics and synbiotics groups reduced significantly compared to the placebo group. The results of meta-analyses on other hormonal and inflammatory indices such as testosterone, DHEAS, GSH, hsCRP, TAC, and hirsutism score showed that there were no significant differences between the intervention and control groups. CONCLUSION Using synbiotics and probiotics in women with polycystic ovary syndrome improve hormonal (FAI, SHBG) and inflammatory (NO, MDA) indices in these patients.
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The treatment with pasireotide in Cushing's disease: effect of long-term treatment on clinical picture and metabolic profile and management of adverse events in the experience of a single center.
Simeoli, C, Ferrigno, R, De Martino, MC, Iacuaniello, D, Papa, F, Angellotti, D, Pivonello, C, Patalano, R, Negri, M, Colao, A, et al
Journal of endocrinological investigation. 2020;(1):57-73
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Abstract
PURPOSES Pasireotide is the first medical therapy officially approved for adult patients with Cushing's disease (CD) experiencing failure of pituitary surgery or not candidates for surgery. The current study aimed at investigating pasireotide effects on clinical picture and metabolic profile in patients enrolled in the phase III CSOM230B2305 trial at Naples center. In addition, the current study focused on safety issues encountered during the study, detailing the management of the different adverse events associated with the treatment with pasireotide in Naples center. METHODS Fourteen patients entered the study; eight patients, receiving pasireotide for at least 6 months, were considered for the efficacy analysis, whereas the entire cohort of 14 patients was considered for the safety analysis. RESULTS Full or partial disease control was obtained in 85.7% of patients, according to a "per-protocol" methodology analysis, and in 42.9% of patients, according to an "intention-to-treat" methodology analysis, after 12 months of treatment. A relevant improvement in clinical signs and symptoms, mainly in facial rubor, supraclavicular fat pad, bruising, hirsutism, and muscle strength was observed; body weight, body mass index, and waist circumference significantly reduced, and a slight non-significant reduction was observed in the prevalence of visceral obesity, hypercholesterolemia, and hypertriglyceridemia. Deterioration of glucose metabolism represented the most common adverse event, occurring in 71.4% of patients, and requiring a dietary regimen as first step, metformin therapy and/or long-acting insulin as second step, and short-acting insulin, as third step; no patients discontinued treatment for hyperglycaemia. Additional adverse events of interest were nausea (21.4%), and vomiting (14.3%), spontaneously resolved in few weeks or some months, except in one patient unsuccessfully treated with metoclopramide and ondansetron, and diarrhoea (14.3%), improved with loperamide treatment. Millimetric gallstones and biliary sludge (7.1%) were managed with ursodeoxycholic acid, inducing lithiasis and biliary sludge resolution, whereas hypocortisolism-related adverse events (7.1%) were resolved with a reduction in the pasireotide dose. CONCLUSIONS The current study on a limited series of patients contributes to confirm that pasireotide may be considered a valid option for treatment of patients with CD, although it requires an appropriate management of adverse events, especially hyperglycaemia.