scholarly journals The Role of Magnesium in Pregnancy and in Fetal Programming of Adult Diseases

2020 ◽  
Author(s):  
Daniela Fanni ◽  
C. Gerosa ◽  
V. M. Nurchi ◽  
M. Manchia ◽  
L. Saba ◽  
...  
Keyword(s):  
Fetal Programming ◽  
Fetal Development ◽  
Normal Values ◽  
Perinatal Period ◽  
Enzymatic Reactions ◽  
Neuromuscular Activity ◽  
Mitochondrial Functions ◽  
Human Pathology ◽  
Magnesium Status

AbstractMagnesium is an essential trace metal and a necessary factor for multiple biochemical functions in humans. Its role in biology is fundamental in over 600 enzymatic reactions implicated in protein synthesis, mitochondrial functions, neuromuscular activity, bone formation, and immune system competence. Magnesium status is relevant in fetal development during gestation and in the newborn growth during the perinatal period. Moreover, magnesium is able to influence fetal programming and disease presentation in childhood or adulthood. The aim of this review is to focus on this metal homeostasis, analyzing its normal values, the causes of hypomagnesemia, the interaction with drugs and other conditions, and the diseases associated with magnesium value alteration during pregnancy, in order to study its role in fetal programming of adult diseases. The data here reported clearly indicated the existence of a connection between magnesium status and human pathology starting from intrauterine life and extending into childhood and adulthood.

Natriuretic Peptides – Addressing the Dilemma of Heart Failure Management

2011 ◽  
Vol 7 (2) ◽  
pp. 104
Author(s):  
Kenneth McDonald ◽  
Ulf Dahlström ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Physical Examination ◽  
Natriuretic Peptides ◽  
Normal Values ◽  
Outpatient Setting ◽  
Heart Failure Management ◽  
Effective Screening ◽  
Specific Symptoms ◽  
Objective Marker

Heart failure (HF) is characterised by non-specific symptoms and unremarkable physical examination; therefore, the need exists for an available objective marker of HF status. Natriuretic peptides (NPs) are a marker that can aid the dilemmas in present-day HF management. More effective screening for clinical deterioration would include changes in brain natriuretic peptide (BNP) levels. Normal values for BNP, <50–100 pg/ml, have excellent negative predictive value (NPV) in excluding HF as a diagnosis. BNP values that are significantly elevated, e.g. >500 pg/ml, make the diagnosis of HF more likely. There are now established and emerging uses for NPs in managing HF in the community. These include the role of NPs at the time of possible new presentation of HF, its role in prognostication and, finally, the increasing interest in using NPs to guide therapy in the outpatient setting.

Cubilin, the Intrinsic Factor-Vitamin B12 Receptor in Development and Disease

2020 ◽  
Vol 27 (19) ◽  
pp. 3123-3150 ◽  
Author(s):  
Renata Kozyraki ◽  
Olivier Cases
Keyword(s):  
Vitamin B12 ◽  
Cancer Progression ◽  
Intrinsic Factor ◽  
Basic Research ◽  
Toxic Substances ◽  
Human Pathology ◽  
Peripheral Membrane Protein ◽  
Epidermal Growth ◽  
Fgf8 Signaling

Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic receptor serving multiple functions in vitamin B12 homeostasis, renal reabsorption of protein or toxic substances including albumin, vitamin D-binding protein or cadmium. Cubilin is a peripheral membrane protein consisting of 8 Epidermal Growth Factor (EGF)-like repeats and 27 CUB (defined as Complement C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at least two molecular partners, Amnionless (AMN) and Lrp2/Megalin. AMN is involved in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for efficient internalization of Cubilin and its ligands. Observations gleaned from animal models with Cubn deficiency or human diseases demonstrate the importance of this protein. In this review addressed to basic research and medical scientists, we summarize currently available data on Cubilin and its implication in renal and intestinal biology. We also discuss the role of Cubilin as a modulator of Fgf8 signaling during embryonic development and propose that the Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects. We finally provide experimental elements suggesting that some aspects of Cubilin physiology might be relevant in drug design.

scholarly journals When a Neonate Is Born, So Is a Microbiota

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 148
Author(s):  
Alessandra Coscia ◽  
Flaminia Bardanzellu ◽  
Elisa Caboni ◽  
Vassilios Fanos ◽  
Diego Giampietro Peroni
Keyword(s):  
Bacterial Colonization ◽  
Perinatal Period ◽  
Delivery Mode ◽  
Fetal Life ◽  
Assisted Reproduction Techniques ◽  
Neonatal Nutrition ◽  
Short And Long Term ◽  
Number Of Bacteria

In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one’s life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the “sterile womb”. Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject.

scholarly journals A Potential Role and Contribution of Androgens in Placental Development and Pregnancy

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 644
Author(s):  
Agata M. Parsons ◽  
Gerrit J. Bouma
Keyword(s):  
Fetal Development ◽  
Fetal Loss ◽  
Membrane Receptors ◽  
Placental Development ◽  
Placental Function ◽  
Fetal Physiology ◽  
Estrogen Synthesis ◽  
And Function ◽  
Pregnancy Disorders

Successful pregnancy requires the establishment of a highly regulated maternal–fetal environment. This is achieved through the harmonious regulation of steroid hormones, which modulate both maternal and fetal physiology, and are critical for pregnancy maintenance. Defects in steroidogenesis and steroid signaling can lead to pregnancy disorders or even fetal loss. The placenta is a multifunctional, transitory organ which develops at the maternal–fetal interface, and supports fetal development through endocrine signaling, the transport of nutrients and gas exchange. The placenta has the ability to adapt to adverse environments, including hormonal variations, trying to support fetal development. However, if placental function is impaired, or its capacity to adapt is exceeded, fetal development will be compromised. The goal of this review is to explore the relevance of androgens and androgen signaling during pregnancy, specifically in placental development and function. Often considered a mere precursor to placental estrogen synthesis, the placenta in fact secretes androgens throughout pregnancy, and not only contains the androgen steroid nuclear receptor, but also non-genomic membrane receptors for androgens, suggesting a role of androgen signaling in placental function. Moreover, a number of pregnancy disorders, including pre-eclampsia, gestational diabetes, intrauterine growth restriction, and polycystic ovarian syndrome, are associated with abnormal androgen levels and androgen signaling. Understanding the role of androgens in the placenta will provide a greater understanding of the pathophysiology of pregnancy disorders associated with androgen elevation and its consequences.

scholarly journals Role of Mitochondria in Viral Infections

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 232
Author(s):  
Srikanth Elesela ◽  
Nicholas W. Lukacs
Keyword(s):  
Viral Infections ◽  
Mitochondrial Dynamics ◽  
The Body ◽  
Viral Diseases ◽  
Multiple Organs ◽  
Innate Immune Signaling ◽  
Mitochondrial Functions ◽  
Host Virus Interactions ◽  
Virus Interactions

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

scholarly journals AIF3 splicing switch triggers neurodegeneration

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shuiqiao Liu ◽  
Mi Zhou ◽  
Zhi Ruan ◽  
Yanan Wang ◽  
Calvin Chang ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Nuclear Translocation ◽  
Chromatin Condensation ◽  
Neuronal Cell ◽  
Adult Brain ◽  
Postmortem Brain ◽  
Mitochondrial Functions

Abstract Background Apoptosis-inducing factor (AIF), as a mitochondrial flavoprotein, plays a fundamental role in mitochondrial bioenergetics that is critical for cell survival and also mediates caspase-independent cell death once it is released from mitochondria and translocated to the nucleus under ischemic stroke or neurodegenerative diseases. Although alternative splicing regulation of AIF has been implicated, it remains unknown which AIF splicing isoform will be induced under pathological conditions and how it impacts mitochondrial functions and neurodegeneration in adult brain. Methods AIF splicing induction in brain was determined by multiple approaches including 5′ RACE, Sanger sequencing, splicing-specific PCR assay and bottom-up proteomic analysis. The role of AIF splicing in mitochondria and neurodegeneration was determined by its biochemical properties, cell death analysis, morphological and functional alterations and animal behavior. Three animal models, including loss-of-function harlequin model, gain-of-function AIF3 knockin model and conditional inducible AIF splicing model established using either Cre-loxp recombination or CRISPR/Cas9 techniques, were applied to explore underlying mechanisms of AIF splicing-induced neurodegeneration. Results We identified a nature splicing AIF isoform lacking exons 2 and 3 named as AIF3. AIF3 was undetectable under physiological conditions but its expression was increased in mouse and human postmortem brain after stroke. AIF3 splicing in mouse brain caused enlarged ventricles and severe neurodegeneration in the forebrain regions. These AIF3 splicing mice died 2–4 months after birth. AIF3 splicing-triggered neurodegeneration involves both mitochondrial dysfunction and AIF3 nuclear translocation. We showed that AIF3 inhibited NADH oxidase activity, ATP production, oxygen consumption, and mitochondrial biogenesis. In addition, expression of AIF3 significantly increased chromatin condensation and nuclear shrinkage leading to neuronal cell death. However, loss-of-AIF alone in harlequin or gain-of-AIF3 alone in AIF3 knockin mice did not cause robust neurodegeneration as that observed in AIF3 splicing mice. Conclusions We identified AIF3 as a disease-inducible isoform and established AIF3 splicing mouse model. The molecular mechanism underlying AIF3 splicing-induced neurodegeneration involves mitochondrial dysfunction and AIF3 nuclear translocation resulting from the synergistic effect of loss-of-AIF and gain-of-AIF3. Our study provides a valuable tool to understand the role of AIF3 splicing in brain and a potential therapeutic target to prevent/delay the progress of neurodegenerative diseases.

scholarly journals The potential role of the Alsberg angle as a predictor of lateral growth disturbance of the capital femoral epiphysis in children with developmental dysplasia of the hip treated by closed reduction

2020 ◽  
Vol 14 (2) ◽  
pp. 106-111 ◽  
Author(s):  
Ronghua Gui ◽  
Federico Canavese ◽  
Shuang Liu ◽  
Lianyong Li ◽  
Lijun Zhang ◽  
...  
Keyword(s):  
Closed Reduction ◽  
Normal Values ◽  
Developmental Dysplasia ◽  
Lateral Growth ◽  
Growth Disturbance ◽  
Level Of Evidence ◽  
Normal Children ◽  
One Year ◽  
Dysplasia Of The Hip

Purpose Early diagnosis and prevention of lateral growth disturbance of the capital femoral epiphysis is challenging after treatment for developmental dysplasia of the hip (DDH). The aim of the study was to evaluate the radiographic changes of the Alsberg angle (AA) in normal children and those with DDH, and to assess the role of AA as a potential predictor of lateral growth disturbance of the capital femoral epiphysis. Methods AA was measured on the anterior-posterior pelvic radiographs of 1000 normal children ranging in age from one to ten years and in 66 children (92 hips) with DDH treated by closed reduction (CR). A comparative analysis was performed. Results In the normal children, mean AA decreased linearly with age, from 76° at age one year to 65° at age ten years, irrespective of gender and laterality. In children with DDH, the average AA was 81.5°(sd 3.9°; 74° to 87°) prior to CR; it was 75.9° (sd 4.5°; 68° to 83°) in normal children of the same age (p < 0.001). Among the 42 children (64 hips) with successfully and uneventfully treated DDH, AA reached normal values between the ages of five and six years. In contrast, children with lateral growth disturbance of the proximal femur physis (24 children, 28 hips) showed significantly higher AA values in comparison with the age-matched controls. Conclusion In DDH patients with successful CR, AA could be expected to match normal values in children between the ages of five and six years. On the other hand, AA can be used as an early predictor for lateral growth disturbance of the capital femoral epiphysis. Level of Evidence Level III

scholarly journals “Newton’s cradle” proton relay with amide–imidic acid tautomerization in inverting cellulase visualized by neutron crystallography

2015 ◽  
Vol 1 (7) ◽  
pp. e1500263 ◽  
Author(s):  
Akihiko Nakamura ◽  
Takuya Ishida ◽  
Katsuhiro Kusaka ◽  
Taro Yamada ◽  
Shinya Fushinobu ◽  
...  
Keyword(s):  
Glycoside Hydrolases ◽  
Side Chain ◽  
Enzymatic Reactions ◽  
X Ray Diffraction ◽  
Peptide Bonds ◽  
Proton Relay ◽  
Newton’S Cradle ◽  
Dynamics Simulations ◽  
Hydrolysis Of

Hydrolysis of carbohydrates is a major bioreaction in nature, catalyzed by glycoside hydrolases (GHs). We used neutron diffraction and high-resolution x-ray diffraction analyses to investigate the hydrogen bond network in inverting cellulase PcCel45A, which is an endoglucanase belonging to subfamily C of GH family 45, isolated from the basidiomycete Phanerochaete chrysosporium. Examination of the enzyme and enzyme-ligand structures indicates a key role of multiple tautomerizations of asparagine residues and peptide bonds, which are finally connected to the other catalytic residue via typical side-chain hydrogen bonds, in forming the “Newton’s cradle”–like proton relay pathway of the catalytic cycle. Amide–imidic acid tautomerization of asparagine has not been taken into account in recent molecular dynamics simulations of not only cellulases but also general enzyme catalysis, and it may be necessary to reconsider our interpretation of many enzymatic reactions.

Effect of Undernutrition During the Perinatal Period on Caries Development in the Rat: II. Caries Susceptibility in Underfed Rats Supplemented with Protein or Caloric Additions During the Suckling Period

1973 ◽  
Vol 52 (4) ◽  
pp. 680-687 ◽  
Author(s):  
Lewis Menaker ◽  
Juan M. Navia
Keyword(s):  
Dental Caries ◽  
Perinatal Period ◽  
Protein Deficiency ◽  
Specific Role ◽  
Protein Supplement ◽  
Distilled Water ◽  
Suckling Period ◽  
Rat Pups ◽  
Low Incidence

The specific role of protein deficiency in altering dental caries incidence in rat pups was investigated. A 10% protein supplement given to undernourished rats during development allowed them to overcome weight deficiencies and reversed dental caries to the low incidence found in well-nourished control rats. Caries in undernourished rats supplemented with an isocaloric, proteinfree solution, was as high as that of undernourished rats intubated with distilled water.

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