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1.
Calcium-phosphate homeostasis in secondary progressive multiple sclerosis patients during mitoxantrone therapy.
Lis, M, Niedziela, N, Nowak-Kiczmer, M, Kubicka-Bączyk, K, Adamczyk-Sowa, M
Neurological research. 2021;(12):1050-1055
Abstract
OBJECTIVES To assess calcium-phosphate parameters in SPMS patients treated with mitoxantrone (MTX). METHODS Thirty eight SPMS patients eligible for MTX therapy in the Department of Neurology in Zabrze, Poland were enrolled in a prospective study from March 2016 to November 2019. The parameters of serum calcium-phosphate metabolism and the neurological status according to the Expanded Disability Status Scale (EDSS) were assessed. In patients with hypovitaminosis D, vitamin D (VitD) supplementation was introduced (4000 IU/day for 1 month and later 2000 IU /day). RESULTS Most patients were women [57.89%]. The mean age [years] was 56.11 (±7.74). The median time from diagnosis to inclusion day (ID) was 7.50 [4.00-14.00] [years]. Due to VitD supplementation, an increase in serum VitD was observed during the study. 84.21% of patients presented with hypovitaminosis D before MTX treatment compared to 47.37% after treatment. Before MTX therapy, none of the patients underwent surgical repair of the fracture compared to 42.11% of patients after MTX treatment (p < 0.01). DISCUSSION Deficiency of VitD was observed at the baseline in most SPMS patients eligible for MTX therapy. Due to adverse reactions to MTX treatment, this therapy requires patient compliance, cautious drug administration and monitoring during the therapy.
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2.
Normal Versus Slowly Processed Pasta and Post-Prandial Glucose Homeostasis in Healthy Subjects: A Pilot Study.
Mengozzi, A, Biancalana, E, Parolini, F, Baldi, S, Raggi, F, Solini, A
Nutrients. 2021;(2)
Abstract
Nutritional science is gaining increasing attention due to the implicit potential to prevent cardio-metabolic diseases. It is also becoming clear that food-making process might influence the metabolic response to the meal. We have conducted a proof-of-concept study to investigate whether slowly processed pasta might positively impact glucose homeostasis. A total of 14 healthy male volunteers underwent two different mixed-meal tests in a randomized order. One meal was composed of 100 g of normally processed pasta and the other 100 g of slowly processed pasta. Each meal was completed with 10 g of olive oil and 10 g of parmesan cheese. Glucose, insulin, and incretin post-prandial responses were assessed at 15, 30, 60, 90, 120, 150, and 180 min. Glucose tolerance, insulin, and incretin response were unaffected by the two different pasta types. However, a slight difference was evident in the shape of the curve of post-prandial insulin (i.e., mildly delayed with the slowly processed pasta). Despite the common belief of a different impact of normally processed and slowly processed pasta on glucose metabolism, they show a superimposable post-prandial metabolic response after a single meal in male healthy individuals. Further studies are required to confirm these results also in chronic, real-life settings and then to translate them to metabolically impaired individuals.
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3.
Dietary Bioactive Ingredients Modulating the cAMP Signaling in Diabetes Treatment.
Wang, Y, Liu, Q, Kang, SG, Huang, K, Tong, T
Nutrients. 2021;(9)
Abstract
As the prevalence of diabetes increases progressively, research to develop new therapeutic approaches and the search for more bioactive compounds are attracting more attention. Over the past decades, studies have suggested that cyclic adenosine monophosphate (cAMP), the important intracellular second messenger, is a key regulator of metabolism and glucose homeostasis in diverse physiopathological states in multiple organs including the pancreas, liver, gut, skeletal muscle, adipose tissues, brain, and kidney. The multiple characteristics of dietary compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the cAMP signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. In this review, we outline the current understanding of the diverse functions of cAMP in different organs involved in glucose homeostasis and show that a diversity of bioactive ingredients from foods activate or inhibit cAMP signaling, resulting in the improvement of the diabetic pathophysiological process. It aims to highlight the diabetes-preventative or -therapeutic potential of dietary bioactive ingredients targeting cAMP signaling.
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4.
Hepatic sinusoids versus central veins: Structures, markers, angiocrines, and roles in liver regeneration and homeostasis.
Mak, KM, Shin, DW
Anatomical record (Hoboken, N.J. : 2007). 2021;(8):1661-1691
Abstract
The blood circulates through the hepatic sinusoids delivering nutrients and oxygen to the liver parenchyma and drains into the hepatic central vein, yet the structures and phenotypes of these vessels are distinctively different. Sinusoidal endothelial cells are uniquely fenestrated, lack basal lamina and possess organelles involved in endocytosis, pinocytosis, degradation, synthesis and secretion. Hepatic central veins are nonfenestrated but are also active in synthesis and secretion. Endothelial cells of sinusoids and central veins secrete angiocrines that play respective roles in hepatic regeneration and metabolic homeostasis. The list of markers for identifying sinusoidal endothelial cells is long and their terminologies are complex. Further, their uses vary in different investigations and, in some instances, could be confusing. Central vein markers are fewer but more distinctive. Here we analyze and categorize the molecular pathways/modules associated with the sinusoid-mediated liver regeneration in response to partial hepatectomy and chemical-induced acute or chronic injury. Similarly, we highlight the findings that central vein-derived angiocrines interact with Wnt/β-catenin in perivenous hepatocytes to direct gene expression and maintain pericentral metabolic zonation. The proposal that perivenous hepatocytes behave as stem/progenitor cells to provoke hepatic homeostatic cell renewal is reevaluated and newer concepts of broad zonal distribution of hepatocyte proliferation in liver homeostasis and regeneration are updated. Thus, this review integrates the structures, biology and physiology of liver sinusoids and central veins in mediating hepatic regeneration and metabolic homeostasis.
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5.
Fungal iron homeostasis with a focus on Aspergillus fumigatus.
Misslinger, M, Hortschansky, P, Brakhage, AA, Haas, H
Biochimica et biophysica acta. Molecular cell research. 2021;(1):118885
Abstract
To maintain iron homeostasis, fungi have to balance iron acquisition, storage, and utilization to ensure sufficient supply and to avoid toxic excess of this essential trace element. As pathogens usually encounter iron limitation in the host niche, this metal plays a particular role during virulence. Siderophores are iron-chelators synthesized by most, but not all fungal species to sequester iron extra- and intracellularly. In recent years, the facultative human pathogen Aspergillus fumigatus has become a model for fungal iron homeostasis of siderophore-producing fungal species. This article summarizes the knowledge on fungal iron homeostasis and its links to virulence with a focus on A. fumigatus. It covers mechanisms for iron acquisition, storage, and detoxification, as well as the modes of transcriptional iron regulation and iron sensing in A. fumigatus in comparison to other fungal species. Moreover, potential translational applications of the peculiarities of fungal iron metabolism for treatment and diagnosis of fungal infections is addressed.
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6.
Anti-cancer actions of carnosine and the restoration of normal cellular homeostasis.
Turner, MD, Sale, C, Garner, AC, Hipkiss, AR
Biochimica et biophysica acta. Molecular cell research. 2021;(11):119117
Abstract
Carnosine is a naturally occurring dipeptide found in meat. Alternatively it can be formed through synthesis from the amino acids, β-alanine and L-histidine. Carnosine has long been advocated for use as an anti-oxidant and anti-glycating agent to facilitate healthy ageing, and there have also been reports of it having anti-proliferative effects that have beneficial actions against the development of a number of different cancers. Carnosine is able to undertake multiple molecular processes, and it's mechanism of action therefore remains controversial - both in healthy tissues and those associated with cancer or metabolic diseases. Here we review current understanding of its mechanistic role in different physiological contexts, and how this relates to cancer. Carnosine turns over rapidly in the body due to the presence of both serum and tissue carnosinase enzymes however, so its use as a dietary supplement would require ingestion of multiple daily doses. Strategies are therefore being developed that are based upon either resistance of carnosine analogs to enzymatic turnover, or else β-alanine supplementation, and the development of these potential therapeutic agents is discussed.
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7.
Iron Homeostasis Disorder and Alzheimer's Disease.
Peng, Y, Chang, X, Lang, M
International journal of molecular sciences. 2021;(22)
Abstract
Iron is an essential trace metal for almost all organisms, including human; however, oxidative stress can easily be caused when iron is in excess, producing toxicity to the human body due to its capability to be both an electron donor and an electron acceptor. Although there is a strict regulation mechanism for iron homeostasis in the human body and brain, it is usually inevitably disturbed by genetic and environmental factors, or disordered with aging, which leads to iron metabolism diseases, including many neurodegenerative diseases such as Alzheimer's disease (AD). AD is one of the most common degenerative diseases of the central nervous system (CNS) threatening human health. However, the precise pathogenesis of AD is still unclear, which seriously restricts the design of interventions and treatment drugs based on the pathogenesis of AD. Many studies have observed abnormal iron accumulation in different regions of the AD brain, resulting in cognitive, memory, motor and other nerve damages. Understanding the metabolic balance mechanism of iron in the brain is crucial for the treatment of AD, which would provide new cures for the disease. This paper reviews the recent progress in the relationship between iron and AD from the aspects of iron absorption in intestinal cells, storage and regulation of iron in cells and organs, especially for the regulation of iron homeostasis in the human brain and prospects the future directions for AD treatments.
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8.
The Role of Obesity-Induced Perivascular Adipose Tissue (PVAT) Dysfunction in Vascular Homeostasis.
Stanek, A, Brożyna-Tkaczyk, K, Myśliński, W
Nutrients. 2021;(11)
Abstract
Perivascular adipose tissue (PVAT) is an additional special type of adipose tissue surrounding blood vessels. Under physiological conditions, PVAT plays a significant role in regulation of vascular tone, intravascular thermoregulation, and vascular smooth muscle cell (VSMC) proliferation. PVAT is responsible for releasing adipocytes-derived relaxing factors (ADRF) and perivascular-derived relaxing factors (PDRF), which have anticontractile properties. Obesity induces increased oxidative stress, an inflammatory state, and hypoxia, which contribute to PVAT dysfunction. The exact mechanism of vascular dysfunction in obesity is still not well clarified; however, there are some pathways such as renin-angiotensin-aldosterone system (RAAS) disorders and PVAT-derived factor dysregulation, which are involved in hypertension and endothelial dysfunction development. Physical activity has a beneficial effect on PVAT function among obese patients by reducing the oxidative stress and inflammatory state. Diet, which is the second most beneficial non-invasive strategy in obesity treatment, may have a positive impact on PVAT-derived factors and may restore the balance in their concentration.
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9.
Vitamin D Effects on Bone Homeostasis and Cardiovascular System in Patients with Chronic Kidney Disease and Renal Transplant Recipients.
Cianciolo, G, Cappuccilli, M, Tondolo, F, Gasperoni, L, Zappulo, F, Barbuto, S, Iacovella, F, Conte, D, Capelli, I, La Manna, G
Nutrients. 2021;(5)
Abstract
Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease-mineral and bone disorder (CKD-MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.
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10.
Natural Molecules Targeting Thioredoxin System and Their Therapeutic Potential.
Zhang, J, Duan, D, Osama, A, Fang, J
Antioxidants & redox signaling. 2021;(14):1083-1107
Abstract
Significance: Thioredoxin (Trx) and thioredoxin reductase are two core members of the Trx system. The system bridges the gap between the universal reducing equivalent NADPH and various biological molecules and plays an essential role in maintaining cellular redox homeostasis and regulating multiple cellular redox signaling pathways. Recent Advance: In recent years, the Trx system has been well documented as an important regulator of many diseases, especially tumorigenesis. Thus, the development of potential therapeutic molecules targeting the system is of great significance for disease treatment. Critical Issues: We herein first discuss the physiological functions of the Trx system and the role that the Trx system plays in various diseases. Then, we focus on the introduction of natural small molecules with potential therapeutic applications, especially the anticancer activity, and review their mechanisms of pharmacological actions via interfering with the Trx system. Finally, we further discuss several natural molecules that harbor therapeutic potential and have entered different clinical trials. Future Directions: Further studies on the functions of the Trx system in multiple diseases will not only improve our understanding of the pathogenesis of many human disorders but also help develop novel therapeutic strategies against these diseases. Antioxid. Redox Signal. 34, 1083-1107.