scholarly journals Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 789 ◽  
Author(s):  
Mattia Bellan ◽  
Laura Andreoli ◽  
Chiara Mele ◽  
Pier Paolo Sainaghi ◽  
Cristina Rigamonti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Convincing Evidence ◽  
In Vivo Studies ◽  
Human Immune System ◽  
Therapeutic Implications ◽  
Wide Range

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

scholarly journals Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 711
Author(s):  
Leticia Diez-Quijada ◽  
Maria del Monte Benítez-González ◽  
María Puerto ◽  
Angeles Jos ◽  
Ana M. Cameán
Keyword(s):  
Immune System ◽  
Scientific Literature ◽  
Anthropogenic Activities ◽  
In Vivo Studies ◽  
Wide Range ◽  
Full Picture ◽  
Underlying Mechanisms ◽  
The Impact

Cyanotoxin occurrence is gaining importance due to anthropogenic activities, climate change and eutrophication. Among them, Microcystins (MCs) and Cylindrospermopsin (CYN) are the most frequently studied due to their ubiquity and toxicity. Although MCs are primary classified as hepatotoxins and CYN as a cytotoxin, they have been shown to induce deleterious effects in a wide range of organs. However, their effects on the immune system are as yet scarcely investigated. Thus, to know the impact of cyanotoxins on the immune system, due to its importance in organisms’ homeostasis, is considered of interest. A review of the scientific literature dealing with the immunotoxicity of MCs and CYN has been performed, and both in vitro and in vivo studies have been considered. Results have confirmed the scarcity of reports on the topic, particularly for CYN. Decreased cell viability, apoptosis or altered functions of immune cells, and changed levels and mRNA expression of cytokines are among the most common effects reported. Underlying mechanisms, however, are still not yet fully elucidated. Further research is needed in order to have a full picture of cyanotoxin immunotoxicity.

Phytochemistry and Pharmacology of the Genus Pedicularis Used in Traditional Chinese Medicine

2014 ◽  
Vol 42 (05) ◽  
pp. 1071-1098 ◽  
Author(s):  
Mao-Xing Li ◽  
Xi-Rui He ◽  
Rui Tao ◽  
Xinyuan Cao
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Chemical Constituents ◽  
Iridoid Glycosides ◽  
In Vivo Studies ◽  
Chemical Components ◽  
Wide Range ◽  
Phenylpropanoid Glycosides

In the present review, the literature data on the chemical constituents and biological investigations of the genus Pedicularis are summarized. Some species of Pedicularis have been widely applied in traditional Chinese medicine. A wide range of chemical components including iridoid glycosides, phenylpropanoid glycosides (PhGs), lignans glycosides, flavonoids, alkaloids and other compounds have been isolated and identified from the genus Pedicularis. In vitro and in vivo studies indicated some monomer compounds and extracts from the genus Pedicularis have been found to possess antitumor, hepatoprotective, anti-oxidative, antihaemolysis, antibacterial activity, fatigue relief of skeletal muscle, nootropic effect and other activities.

scholarly journals The Efficacy of Nanoemulsion-Based Delivery to Improve Vitamin D Absorption: Comparison of In Vitro and In Vivo Studies

2018 ◽  
Vol 62 (4) ◽  
pp. 1700836 ◽  
Author(s):  
Alagu Selvi Kadappan ◽  
Chi Guo ◽  
Cansu E. Gumus ◽  
Amy Bessey ◽  
Richard J. Wood ◽  
...  
Keyword(s):  
Vitamin D ◽  
In Vivo Studies

scholarly journals Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 161
Author(s):  
Séverine André ◽  
Lionel Larbanoix ◽  
Sébastien Verteneuil ◽  
Dimitri Stanicki ◽  
Denis Nonclercq ◽  
...  
Keyword(s):  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Therapeutic Agents ◽  
In Vivo Studies ◽  
Phage Display Technology ◽  
Brain Penetration ◽  
Wide Range ◽  
The Brain

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide.

scholarly journals Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1232
Author(s):  
Stefania D’Adamo ◽  
Silvia Cetrullo ◽  
Veronica Panichi ◽  
Erminia Mariani ◽  
Flavio Flamigni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Antioxidant Activities ◽  
Synergistic Effects ◽  
National Health System ◽  
Bioactive Molecules ◽  
Joint Disease ◽  
In Vivo Studies ◽  
Wide Range

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.

scholarly journals Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 596 ◽  
Author(s):  
María del Carmen Villegas-Aguilar ◽  
Álvaro Fernández-Ochoa ◽  
María de la Luz Cádiz-Gurrea ◽  
Sandra Pimentel-Moral ◽  
Jesús Lozano-Sánchez ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Phenolic Compounds ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Wide Range ◽  
High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

scholarly journals Vitamin D and prostate cancer

2013 ◽  
Vol 66 (5-6) ◽  
pp. 259-262
Author(s):  
Goran Marusic ◽  
Dimitrije Jeremic ◽  
Sasa Vojinov ◽  
Natasa Filipovic ◽  
Milan Popov
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Physiological Role ◽  
In Vivo Studies ◽  
Vitamin D Metabolism ◽  
Genetic Changes ◽  
Metabolic Role

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed.

scholarly journals Critical Roles of Kisspeptins in Female Puberty and Preovulatory Gonadotropin Surges as Revealed by a Novel Antagonist

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 722-730 ◽  
Author(s):  
R. Pineda ◽  
D. Garcia-Galiano ◽  
A. Roseweir ◽  
M. Romero ◽  
M. A. Sanchez-Garrido ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Female Rat ◽  
Female Reproduction ◽  
Gonadotropin Secretion ◽  
Therapeutic Implications ◽  
Intracerebroventricular Infusion ◽  
Puberty Onset ◽  
The Impact

Kisspeptins (Kp) have recently emerged as master regulators of the reproductive axis and among the most potent elicitors of GnRH-gonadotropin secretion. Despite their paramount importance in reproductive physiology and their potential therapeutic implications, development of Kp antagonists has remained elusive, and only recently has the first compound with the ability to block Kp actions in vitro and in vivo, namely p234, been reported. However, previous in vivo studies all used acute central injections, whereas characterization of the effects of the antagonist after continuous or systemic administration, which poses pharmacological challenges, is still pending. We report herein a comprehensive series of analyses on the impact of continuous intracerebroventricular infusion of p234 on puberty onset and the preovulatory surge of gonadotropins in the female rat. In addition, the effects of systemic (ip) administration of a tagged p234-penetratin, with a predicted higher permeability at the blood-brain barrier, on Kp-10 induced gonadotropin secretion were evaluated. Central infusion of p234 to pubertal females delayed vaginal opening and decreased uterine and ovarian weights at the expected time of puberty, without affecting body weight. Likewise, chronic intracerebroventricular administration of p234 for 4 d prevented the preovulatory surges of LH and FSH. In addition, systemic (ip) administration of p234-penetratin significantly attenuated acute LH and FSH responses to Kp-10, either after intracerebroventricular or ip injection of Kp. Our data document the validity of p234 for antagonizing Kp actions in vivo and provide direct experimental evidence for the important role of Kp signaling in the key events of female reproduction, such as puberty onset and the preovulatory surge of gonadotropins.

The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands

2007 ◽  
Vol 292 (5) ◽  
pp. F1390-F1395 ◽  
Author(s):  
M. E. Rodriguez ◽  
Y. Almaden ◽  
S. Cañadillas ◽  
A. Canalejo ◽  
E. Siendones ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Parathyroid Tissue ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
In Vivo Studies ◽  
Control Treatment ◽  
Maximum Increase

We previously demonstrated that extracellular calcium regulates vitamin D receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568 potentiates the effects of calcium on the calcium-sensing receptor, it was hypothesized that administration of R-568 may result in increased VDR expression in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and protein were conducted in cultures of whole rat parathyroid glands and human hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the effect of R-568 and calcitriol alone and in combination. Incubation of rat parathyroid glands in vitro with R-568 (0.001–1 μM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR expression (mean ± SE). Incubation in 1 mM calcium + 0.001 μM R-568 elicited an increase in VDR mRNA (306 ± 46%) similar to the maximum increase detected with 1.5 mM calcium (330 ± 42%). In vivo, VDR mRNA was increased after administration of R-568 (168 ± 9%, P < 0.001 vs. control) or calcitriol (198 ± 16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in normal rat parathyroid glands and in human parathyroid glands with diffuse, but not nodular, hyperplasia. In conclusion, the present study shows that the calcimimetic R-568 exerts a stimulatory effect on VDR expression in the parathyroid glands of study models and provides additional evidence for the use of calcimimetics in the treatment of secondary hyperparathyroidism.

scholarly journals Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation

2018 ◽  
Author(s):  
Vinicius Cruzat ◽  
Marcelo Macedo Rogero ◽  
Kevin Noel Keane ◽  
Rui Curi ◽  
Philip Newsholme
Keyword(s):  
Amino Acid ◽  
The Body ◽  
Glutamine Metabolism ◽  
In Vivo Studies ◽  
Glutamine Supplementation ◽  
Bacterial Killing ◽  
Nutrition Supplementation ◽  
Wide Range

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

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