Search Results (8)

Mammalian cells require iron to satisfy their metabolic needs and to accomplish specialized functions, such as hematopoiesis, mitochondrial biogenesis, energy metabolism, or oxygen transport. Iron homeostasis is balanced by the interplay of proteins responsible for iron import, storage, and export. A misbalance of iron homeostasis may cause either iron deficiencies or iron overload diseases. The clinical work-up of iron dysregulation is highly important, as severe symptoms and pathologies may arise. Treating iron overload or iron deficiency is important to avoid cellular damage and severe symptoms and improve patient outcomes. The impressive progress made in the past years in understanding mechanisms that maintain iron homeostasis has already changed clinical practice for treating iron-related diseases and is expected to improve patient management even further in the future. Full article

This paper investigates the strategies and priorities to identify the critical indicators for the protection of the environment and ecosystem in the mountain regions of southwest Saudi Arabia, considering the natural resources, renewable energy potential, local economy, urban development issues, and compatibility with the Saudi Vision 2030. The southern region of the country is characterized as having cooler climatic conditions than the other regions of Saudi Arabia and is rich in natural resources and renewable energy potential. It also has potential in the sectors of agriculture, forests, and animal production, and the region’s heritage is valuable for its tourism industry. During the past years, the region is experiencing a misbalance in its resources and population due to a quick increase in urban development. It is seen that there has been no strategy in place for the management of development. Hence, it is important to establish a framework designed to manage urban planning and sprawl that considers the topographical conditions, wildlife and forest protection, and investment in natural and renewable resources. This study employs a focus group approach to investigate these issues. Different expert panels were invited to Al-Baha University in December 2019 to discuss the sustainable development priorities of Saudi Arabia’s southern regions. These included decision-makers from governmental sectors, and academics from the university’s faculties of engineering, economics, sciences, and social sciences. The study highlights the issues of urban sprawl management in cities that impact the environmental conditions and wildlife habitat, concluding that the agriculture and tourism industries are the most important factors that should be targeted by developers in the southwestern regions of the country. Full article

End-stage kidney disease is preferably treated by kidney transplantation. The suboptimal function of the allograft often results in misbalances in kidney-controlled processes and requires long-term monitoring of allograft function and viability. As the kidneys are organs with a very high metabolomic rate, a metabolomics approach is suitable to describe systematic changes in post-transplant patients and has great potential for monitoring allograft function, which has not been described yet. In this study, we used blood plasma samples from 55 patients after primary kidney transplantation identically treated with immunosuppressants with follow-up 50 months in the mean after surgery and evaluated relative levels of basal plasma metabolites detectable by NMR spectroscopy. We were looking for the correlations between circulating metabolites levels and allograft performance and allograft rejection features. Our results imply a quantitative relationship between restricted renal function, insufficient hydroxylation of phenylalanine to tyrosine, lowered renal glutamine utilization, shifted nitrogen balance, and other alterations that are not related exclusively to the metabolism of the kidney. No link between allograft function and energy metabolism can be concluded, as no changes were found for glucose, glycolytic intermediates, and 3-hydroxybutyrate as a ketone body representative. The observed changes are to be seen as a superposition of changes in the comprehensive inter-organ metabolic exchange, when the restricted function of one organ may induce compensatory effects or cause secondary alterations. Particular differences in plasma metabolite levels in patients with acute cellular and antibody-mediated allograft rejection were considered rather to be related to the loss of kidney function than to the molecular mechanism of graft rejection since they largely follow the alterations observed by restricted allograft function. In the end, we showed using a simple mathematical model, multilinear regression, that the basal plasmatic metabolites correlated with allograft function expressed by the level of glomerular filtration rate (with creatinine: p-value = 4.0 × 10⁻²⁶ and r = 0.94, without creatinine: p-value = 3.2 × 10⁻²² and r = 0.91) make the noninvasive estimation of the allograft function feasible. Full article

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver. Full article

Steam network operation stability and reliability is vital for any industrial branch. A combined steam network model comprising a balance and a coupled thermo-hydrodynamic model, including seasonal variations impact and system specificities, is presented. A balance model can readily be used by a refinery’s operators. The thermo-hydrodynamic model identifies system bottlenecks and cold spots and evaluates proposed operation and investment measures including heat loss reduction. A three-pressure levels refinery steam network served for model testing and validation. Balance model results reveal significant misbalance in steam production and consumption, reaching 30.5% in the low-pressure steam system, and heat balance differences in the range of 9.2% to 29.5% on individual pressure levels, attributable both to flow measurement accuracy issues and to heat losses. The thermo-hydrodynamic model results differ from the measured steam parameters by less than 5% (temperature) and by less than 4% (pressure), respectively, with the estimated operational insulation heat conductivity exceeding 0.08 W/m/K. Its comparison with that of 0.03 W/m/K for dry insulation material yields the need for pipelines re-insulation and a partial revamp of the steam network. The model is sufficiently general for any type of industry, pursuing the goal of cleaner and energy-efficient steam transport and consumption. Full article

Glucose withdrawal has been used as a model for the study of homeostatic defense mechanisms, especially for how cells cope with a shortage of nutrient supply by enhancing catabolism. However, detailed cellular responses to glucose withdrawal have been poorly studied, and are controversial. In this study, we determined how glucose withdrawal affects mitochondrial activity, and the quantity and the role of SIRT1 in these changes. The results of our study indicate a substantial increase in ATP production from mitochondria, through an elevation of mitochondrial biogenesis, mediated by SIRT1 activation that is driven by increased NAD⁺/NADH ratio. Moreover, mitochondria persisted in the cells as elongated forms, and apparently evaded mitophagic removal. This led to a steady increase in mitochondria content and the reactive oxygen species (ROS) generated from them, indicating failure in ATP and ROS homeostasis, due to a misbalance in SIRT1-mediated mitochondria turnover in conditions of glucose withdrawal. Our results suggest that SIRT1 activation alone cannot properly manage energy homeostasis under certain metabolic crisis conditions. Full article

Obesity represents an abnormal fat accumulation resulting from energy imbalances. It represents a disease with heavy consequences on population health and society economy due to its related morbidities and epidemic proportion. Defining and classifying obesity and its related parameters of evaluation is the first challenge toward understanding this multifactorial health problem. Therefore, within this review we report selected illustrative examples of the underlying mechanisms beyond the obesity pathogenesis which is systemic rather than limited to fat accumulation. We also discuss the gut-brain axis and hormones as the controllers of energy homeostasis and report selected impacts of obesity on the key metabolic tissues. The concepts of “broken energy balance” is detailed as the obesity starting key step. Sleep shortage and psychological factors are also reported with influences on obesity development. Importantly, describing such mechanistic pathways would allow clinicians, biologists and researchers to develop and optimize approaches and methods in terms of diagnosis, classification, clinical evaluation, treatment and prognosis of obesity. Full article

Mesocestoides vogae larvae represent a suitable model for evaluating the larvicidal potential of various compounds. In this study we investigated the in vitro effects of three natural flavonolignans—silybin (SB), 2,3-dehydrosilybin (DHSB) and silychristin (SCH)—on M. vogae larvae at concentrations of 5 and 50 μM under aerobic and hypoxic conditions for 72 h. With both kinds of treatment, the viability and motility of larvae remained unchanged, metabolic activity, neutral red uptake and concentrations of neutral lipids were reduced, in contrast with a significantly elevated glucose content. Incubation conditions modified the effects of individual FLs depending on their concentration. Under both sets of conditions, SB and SCH suppressed metabolic activity, the concentration of glucose, lipids and partially motility more at 50 μM, but neutral red uptake was elevated. DHSB exerted larvicidal activity and affected motility and neutral lipid concentrations differently depending on the cultivation conditions, whereas it decreased glucose concentration. DHSB at the 50 μM concentration caused irreversible morphological alterations along with damage to the microvillus surface of larvae, which was accompanied by unregulated neutral red uptake. In conclusion, SB and SCH suppressed mitochondrial functions and energy stores, inducing a physiological misbalance, whereas DHSB exhibited a direct larvicidal effect due to damage to the tegument and complete disruption of larval physiology and metabolism. Full article