Contribution to diagnostics/prognostics of tuberculosis in children. II. Indicative value of metal ions and biochemical parameters in serum

Luterotti, Svjetlana; Kordić, Tončica Vukman; Letoja, Ivka Zoričić; Dodig, Slavica

doi:10.1515/acph-2015-0027

Cited by 7 publications

(6 citation statements)

References 12 publications

(14 reference statements)

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“…Elevated serum Cu/Zn ratio is indicative of nutritional deficiencies, oxidative stress, inflammation, and immune abnormalities [ 290 ], contributing to an increased risk of all-cause, cancer, and cardiovascular-related mortalities [ 291 ]. It also serves as a common biomarker of frailty linked with multiple-cause mortality in the elderly and of advancement of chronic disease [ 292 , 293 ] but also as a biomarker for children predisposed for numerous pediatric diseases, including vascular complications, cancers, and virus infections, and for neonates with early-onset congenital infections [ 294 , 295 , 296 , 297 , 298 ]. What leads to altered plasma Cu/Zn ratios is still, however, unknown [ 299 ].…”

Section: Resultsmentioning

confidence: 99%

Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates

Monette

Mouland

2020

Viruses

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Liquid-liquid phase separation (LLPS) is a rapidly growing research focus due to numerous demonstrations that many cellular proteins phase-separate to form biomolecular condensates (BMCs) that nucleate membraneless organelles (MLOs). A growing repertoire of mechanisms supporting BMC formation, composition, dynamics, and functions are becoming elucidated. BMCs are now appreciated as required for several steps of gene regulation, while their deregulation promotes pathological aggregates, such as stress granules (SGs) and insoluble irreversible plaques that are hallmarks of neurodegenerative diseases. Treatment of BMC-related diseases will greatly benefit from identification of therapeutics preventing pathological aggregates while sparing BMCs required for cellular functions. Numerous viruses that block SG assembly also utilize or engineer BMCs for their replication. While BMC formation first depends on prion-like disordered protein domains (PrLDs), metal ion-controlled RNA-binding domains (RBDs) also orchestrate their formation. Virus replication and viral genomic RNA (vRNA) packaging dynamics involving nucleocapsid (NC) proteins and their orthologs rely on Zinc (Zn) availability, while virus morphology and infectivity are negatively influenced by excess Copper (Cu). While virus infections modify physiological metal homeostasis towards an increased copper to zinc ratio (Cu/Zn), how and why they do this remains elusive. Following our recent finding that pan-retroviruses employ Zn for NC-mediated LLPS for virus assembly, we present a pan-virus bioinformatics and literature meta-analysis study identifying metal-based mechanisms linking virus-induced BMCs to neurodegenerative disease processes. We discover that conserved degree and placement of PrLDs juxtaposing metal-regulated RBDs are associated with disease-causing prion-like proteins and are common features of viral proteins responsible for virus capsid assembly and structure. Virus infections both modulate gene expression of metalloproteins and interfere with metal homeostasis, representing an additional virus strategy impeding physiological and cellular antiviral responses. Our analyses reveal that metal-coordinated virus NC protein PrLDs initiate LLPS that nucleate pan-virus assembly and contribute to their persistence as cell-free infectious aerosol droplets. Virus aerosol droplets and insoluble neurological disease aggregates should be eliminated by physiological or environmental metals that outcompete PrLD-bound metals. While environmental metals can control virus spreading via aerosol droplets, therapeutic interference with metals or metalloproteins represent additional attractive avenues against pan-virus infection and virus-exacerbated neurological diseases.

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Section: Resultsmentioning

confidence: 99%

Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates

Monette

Mouland

2020

Viruses

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“…Due to higher levels of Zn in the hair of myopic children, surprisingly, Cu/Zn ratio was significantly smaller in the myopic group of our research. Cu/Zn ratio has been proven of diagnostic value in a number of human disorders, including pediatric infectious diseases, such as tuberculosis [35]. The diagnostic value of the Cu/Zn ratio as a disease marker was also shown in hypertension, autism, and neoplastic diseases [36–38].…”

Section: Discussionmentioning

confidence: 99%

Concentration of Zinc, Copper, Selenium, Manganese, and Cu/Zn Ratio in Hair of Children and Adolescents with Myopia

Fedor

Urban

Socha

et al. 2019

Journal of Ophthalmology

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The aim of this work was to determine the concentration of trace elements, zinc, copper, selenium, manganese, and Cu/Zn ratio, in scalp hair samples of children and adolescents with myopia. The study included 92 children (mean age 14.5 ± 2.5 years) with myopia and 43 healthy persons (mean age 11.8 ± 4.7 years). Each patient had a complete eye examination. Trace element concentrations in hair were determined by atomic absorption spectrometry. Cu/Zn ratio was also calculated. The zinc level in the hair of myopic patients was significantly higher (260 µg/g) in comparison to the control group (130 µg/g). There was a significantly lower Cu/Zn ratio in myopic patients (0.045) compared with controls (0.07). An insignificant difference was observed in the hair level of copper, selenium, and manganese between patients and controls. The results show that trace elements may play a significant role in the pathogenesis of myopia. Further studies should pay more attention to determine the effect of trace element on children myopia.

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“…Importantly, the inverse regulation of plasma Cu and Zn is a well-established characteristic of infections, and the Cu/Zn ratio has been proven of diagnostic value in a number of human disorders, including pediatric infectious diseases, such as giardiasis or amebiasis [20] and tuberculosis [23,36]. Furthermore, the diagnostic value of the Cu/Zn ratio as a disease marker was also shown in autism, attention-deficit hyperactivity disorder, hypertension, inflammatory, as well as neoplastic diseases [33,37,38,39].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the Cu/Zn ratio is altered in certain diseases [19,20,21,22,23]. Therefore, we postulated that infections disrupt homeostasis of the trace elements Cu and Zn in neonates.…”

Section: Introductionmentioning

confidence: 99%

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

et al. 2017

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Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections.

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Contribution to diagnostics/prognostics of tuberculosis in children. II. Indicative value of metal ions and biochemical parameters in serum

Cited by 7 publications

References 12 publications

Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates

Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates

Concentration of Zinc, Copper, Selenium, Manganese, and Cu/Zn Ratio in Hair of Children and Adolescents with Myopia

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

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