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Nature Communications Sep 2023Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether...
Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether zinc and the AHR pathway are linked. We show that dietary supplementation with an AHR pre-ligand offers protection against inflammatory bowel disease in a mouse model while protection fails in mice lacking AHR in the intestinal epithelium. AHR agonist treatment is also ineffective in mice fed zinc depleted diet. In human ileum organoids and Caco-2 cells, AHR activation increases total cellular zinc and cytosolic free Zn concentrations through transcription of genes for zinc importers. Tight junction proteins are upregulated through zinc inhibition of nuclear factor kappa-light-chain-enhancer and calpain activity. Our data show that AHR activation by plant-derived dietary ligands improves gut barrier function at least partly via zinc-dependent cellular pathways, suggesting that combined dietary supplementation with AHR ligands and zinc might be effective in preventing inflammatory gut disorders.
Topics: Humans; Animals; Mice; Receptors, Aryl Hydrocarbon; Zinc; Caco-2 Cells; Ligands; Cytosol; Organic Chemicals
PubMed: 37669965
DOI: 10.1038/s41467-023-41168-y -
Biometals : An International Journal on... Aug 2023In the genus Pseudomonas, zinc homeostasis is mediated by a complete set of import and export systems, whose expression is precisely controlled by three transcriptional... (Review)
Review
In the genus Pseudomonas, zinc homeostasis is mediated by a complete set of import and export systems, whose expression is precisely controlled by three transcriptional regulators: Zur, CzcR and CadR. In this review, we describe in detail our current knowledge of these systems, their regulation, and the biological significance of zinc homeostasis, taking Pseudomonas aeruginosa as our paradigm. Moreover, significant parts of this overview are dedicated to highlight interactions and cross-regulations between zinc and copper import/export systems, and to shed light, through a review of the literature and comparative genomics, on differences in gene complement and function across the whole Pseudomonas genus. The impact and importance of zinc homeostasis in Pseudomonas and beyond will be discussed throughout this review.
Topics: Pseudomonas; Zinc; Homeostasis; Pseudomonas aeruginosa; Copper; Bacterial Proteins; Gene Expression Regulation, Bacterial
PubMed: 36472780
DOI: 10.1007/s10534-022-00475-5 -
Frontiers in Endocrinology 2023Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the... (Review)
Review
Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the work of many organs and systems of the body, including the immune system and the thyroid gland, and a violation of their supply can be the cause of pathological changes in them. In pathology, the interaction between thyroid hormones (TG), minerals and the immune system is disturbed. The review of the literature examines the immunomodulatory role of TG, minerals, their properties, and their participation in the pathogenesis of autoimmune thyroid diseases (AITD). The study of the relationship between the excess or deficiency of minerals and AITD is described. The basis of the development of AITD - Hashimoto's thyroiditis (HT), Graves' disease (GD), Graves' ophthalmopathy (GO) is the loss of immune tolerance to thyroid antigens - thyroid peroxidase (TPO), thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R). Immune-mediated mechanisms - production of autoantibodies to thyroid antigens and lymphocytic thyroid infiltration - are involved in the pathogenesis of AITD. Insufficiency of regulatory T cells (Treg) and regulatory B cells (Breg), imbalance between Th17-lymphocytes and Treg-lymphocytes, abnormal production of pro-inflammatory cytokines has a significant influence on the progression of AITD. With AITD, the balance between oxidants and antioxidants is disturbed and oxidative stress (OS) occurs. The lack of modern effective pharmacological therapy of AITD prompted us to consider the mechanisms of influence, possibilities of immunocorrection of pathogenetic factors using TG, micro/macronutrients. In order to develop a more effective treatment strategy, as well as approaches to prevention, a critical analysis of the ways of immunotherapeutic use of dietary supplements of I, Se, Zn, Mg and other minerals in AITD was carried out.
Topics: Humans; Thyroid Hormones; Hashimoto Disease; Zinc; Selenium; Magnesium
PubMed: 37711890
DOI: 10.3389/fendo.2023.1225494 -
Theranostics 2023Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications. Conventional drug applications usually focus on a...
Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications. Conventional drug applications usually focus on a single treatment target, and the penetration depth restricts the post-delivery effect. We fabricated a curcumin-zinc framework (ZnMOF) encapsulated gamma-polyglutamic acid (γ-PGA) microneedle patch (ZnMOF-MN) as a multifunctional biosafe transdermal drug delivery system. ZnMOF was characterized with the field emission scanning electron microscope (FE-SEM), dynamic light scattering (DLS), elemental mapping, and X-ray diffraction (XRD). The topographical and hygroscopic features of ZnMOF-MN were characterized with SEM. The ZnMOF release profile and the penetration of ZnMOF-MN were also evaluated. The anti-oxidant, anti-apoptosis, and antiandrogen effects of ZnMOF solution and ZnMOF-MN extract were studied on mouse dermal papilla cells (DPCs). Two animal models (in C57BL/6 mice), including androgenic alopecia (AGA) model and wound healing model, were used to identify the therapeutic effect of ZnMOF-MN on hair regrowth and wound healing . Hair follicles, surrounding vessels (CD31+), and proliferating cells (Ki67+) were evaluated by histological staining. ZnMOF crystals were cone-shaped nanoparticles with a size distribution of 424.9 ± 59.01 nm. ZnMOF-MN patch can create temporary holes in the skin to directly and evenly deliver bioactive ZnMOF particles to the targeted depth and achieve a steady and sustained release of Zn and curcumin. , ZnMOF significantly improved the viability of DPCs against the excess reactive oxygen species (ROS) and inhibited the apoptosis induced by zinc deficiency. In addition, it also reversed the inhibitory effects of dihydrotestosterone (DHT) infiltration. Moreover, the ZnMOF-MN treatment has been proved to accelerate wound healing and increase hair follicles in wound healing models, and improved the hair regrowth in AGA animal models. Enhanced capillary density and cell proliferation observed in the CD31+ and Ki67+ staining of ZnMOF-MN group in both animal models also suggested that ZnMOF can facilitate angiogenesis and promote cell proliferation in the skin, respectively. The ZnMOF-MN treatment is a comprehensive solution with excellent therapeutic efficacy and patient-friendly features for promoting hair growth under various clinical conditions.
Topics: Mice; Animals; Curcumin; Zinc; Ki-67 Antigen; Mice, Inbred C57BL; Hair; Alopecia; Drug Delivery Systems; Organic Chemicals
PubMed: 37441591
DOI: 10.7150/thno.84118 -
Nutrients Oct 2023This Special Issue of 'Dietary Supplements and Musculoskeletal Health and Function' provides new insights into the use of a wide range of dietary supplements, such as...
This Special Issue of 'Dietary Supplements and Musculoskeletal Health and Function' provides new insights into the use of a wide range of dietary supplements, such as zinc, creatine, Vitamin D, HMB, BCAA, betaine, glucoraphanin, citrulline and collagen, to improve bone and muscle structure and function [...].
Topics: Dietary Supplements; Vitamins; Vitamin D; Creatine; Zinc
PubMed: 37892478
DOI: 10.3390/nu15204404 -
Clinical and Experimental Medicine Feb 2024This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses... (Review)
Review
This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses zinc-related pathological states. Zinc cannot be stored in significant amounts, so regular dietary intake is essential. ZIP4 and/or ZnT5B transport dietary zinc ions from the duodenum into the enterocyte, ZnT1 transports zinc ions from the enterocyte into the circulation, and ZnT5B (bidirectional zinc transporter) facilitates endogenous zinc secretion into the intestinal lumen. Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability. In circulation, 70% of zinc is bound to albumin, and the majority in the body is found in skeletal muscle and bone. Zinc excretion is via faeces (predominantly), urine, sweat, menstrual flow and semen. Excessive zinc intake can inhibit the absorption of copper and iron, leading to copper deficiency and anaemia, respectively. Zinc toxicity can adversely affect the lipid profile and immune system, and its treatment depends on the mode of zinc acquisition. Acquired zinc deficiency usually presents later in life alongside risk factors like malabsorption syndromes, but medications like diuretics and angiotensin-receptor blockers can also cause zinc deficiency. Inherited zinc deficiency condition acrodermatitis enteropathica, which occurs due to mutation in the SLC39A4 gene (encoding ZIP4), presents from birth. Treatment involves zinc supplementation via zinc gluconate, zinc sulphate or zinc chloride. Notably, oral zinc supplementation may decrease the absorption of drugs like ciprofloxacin, doxycycline and risedronate.
Topics: Humans; Copper; Zinc; Intestines; Ions; Cation Transport Proteins; Acrodermatitis
PubMed: 38367035
DOI: 10.1007/s10238-024-01302-6 -
Nutrients Sep 2023The benefits of zinc in treating certain gastrointestinal (GI) diseases have been recognized for over two decades. This review aims to explore zinc deficiency (ZD) and... (Review)
Review
The benefits of zinc in treating certain gastrointestinal (GI) diseases have been recognized for over two decades. This review aims to explore zinc deficiency (ZD) and the potential therapeutic value and safety of zinc supplementation in pediatric GI diseases. A systematic review of published articles on ZD and zinc as adjuvant treatments for GI diseases was conducted using various databases. Children with inflammatory bowel disease (IBD), celiac disease, and those receiving long-term proton pump inhibitor treatments are particularly susceptible to ZD. ZD in children with celiac disease and IBD is attributed to insufficient intake, reduced absorption, and increased intestinal loss as a result of the inflammatory process. Zinc plays a crucial role in maintaining the integrity of the gastric mucosa and exerts a gastroprotective action against gastric lesions. Although considerable evidence supports the use of zinc as adjuvant therapy for certain GI diseases in adults, its use is unspecified in children except for infectious diarrhea. Current evidence suggests that zinc supplementation with well-documented dosages helps reduce the duration of diarrhea in children with acute or persistent diarrhea, while there are no specific guidelines for zinc supplementation in children with IBD and celiac disease. Zinc supplementation appears to be beneficial in peptic ulcer disease or gastroesophageal reflux disease. The available evidence highlights the need for intervention programs to enhance zinc status and reduce the morbidity of certain GI diseases in children.
Topics: Adult; Child; Humans; Zinc; Celiac Disease; Diarrhea; Dietary Supplements; Inflammatory Bowel Diseases
PubMed: 37836377
DOI: 10.3390/nu15194093 -
International Breastfeeding Journal Jun 2023Global estimates of calcium, zinc and vitamin D content in breastmilk are lacking. The objective of this systematic review was to determine the calcium, zinc, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Global estimates of calcium, zinc and vitamin D content in breastmilk are lacking. The objective of this systematic review was to determine the calcium, zinc, and vitamin D content in breast milk.
METHODS
A systematic search of the online databases Embase, MEDLINE, and CENTRAL was conducted in November 2022 and complemented by searches of the African Journals Online database and the LILACS database, and reference lists. Studies reporting the calcium, zinc and vitamin D content in breast milk of apparently healthy mothers and infants were included. Random effects meta-analyses were conducted. The effect of influencing factors were investigated with sub-group analyses and meta-regressions.
RESULTS
A total of 154 studies reporting on breast milk calcium were identified, with a mean calcium concentration in breast milk of 261 mg/L (95% CI: 238, 284). Calcium concentration was influenced by maternal health and decreased linearly over the duration of lactation. Calcium concentration at a specific time during lactation could be estimated with the equation: calcium concentration [mg/L] = 282 - 0.2331 ✕ number of days since birth. A total of 242 studies reporting on breast milk zinc were identified, with a mean zinc concentration of 2.57 mg/L (95% CI: 2.50, 2.65). Zinc concentration was influenced by several factors, such as maternal age, gestational age, and maternal diet. Zinc concentration started high in the first weeks post-partum followed by a rapid decrease over the first months. Zinc concentration at a specific time during lactation could be estimated with the equation: zinc concentration [mg/L] = 6 + 0.0005 ✕ days - 2.0266 ✕ log(days). A total of 43 studies reporting on breast milk vitamin D were identified, with a mean total antirachitic activity of breast milk of 58 IU/L (95% CI: 45, 70), which consisted mostly of 25OHD3, and smaller amounts of vitamin D3, 25OHD2 and vitamin D2. Vitamin D concentration showed wide variations between studies and was influenced by vitamin D supplementation, continent and season.
CONCLUSIONS
This review provides global estimates of calcium, zinc and vitamin D content in breast milk, as well as indications on changes over time and depending on influencing factors.
Topics: Infant; Female; Humans; Milk, Human; Calcium; Breast Feeding; Zinc; Vitamin D; Vitamins; Dietary Supplements
PubMed: 37264448
DOI: 10.1186/s13006-023-00564-2 -
Nutrients Aug 2023Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the prevalence of which has increased in children and adolescents over the years. Studies point to... (Review)
Review
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the prevalence of which has increased in children and adolescents over the years. Studies point to deficiency of trace elements as one of the factors involved in the etiology of the disorder, with zinc being one of the main trace elements investigated in individuals with ASD. The aim of this review is to summarize scientific evidence about the relationship between zinc status and ASD in children and adolescents. This review has been registered in the International Prospective Register of Systematic Reviews (registration number CRD42020157907). The methodological guidelines adopted were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were selected from an active investigation of the PubMed, Scopus, LILACS, and Google databases to search for observational studies. Fifty-two studies from twenty-two countries were included. The sample sizes ranged from 20 to 2635, and the participants ranged from 2 to 18 years old. Nine types of biological matrices were used, with hair, serum, and plasma being the most frequently used in the evaluation of zinc concentrations. Significant differences in zinc concentrations between the ASD and control groups were observed in 23 studies, of which 19 (36%) showed lower zinc concentrations in the ASD group. The classification of studies according to methodological quality resulted in high, moderate, and low quality in 10, 21, and 21 studies, respectively. In general, we did not observe a significant difference between zinc concentrations of children and adolescents with ASD compared to controls; however, studies point to an occurrence of lower concentrations of Zn in individuals with ASD. This review reveals that more prospective studies with greater methodological rigor should be conducted in order to further characterize this relation.
Topics: Humans; Adolescent; Child; Child, Preschool; Zinc; Trace Elements; Autism Spectrum Disorder; Prospective Studies; Databases, Factual
PubMed: 37630853
DOI: 10.3390/nu15163663 -
International Journal of Molecular... Oct 2023Trace elements and metals play critical roles in the normal functioning of the central nervous system (CNS), and their dysregulation has been implicated in... (Review)
Review
Trace elements and metals play critical roles in the normal functioning of the central nervous system (CNS), and their dysregulation has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In a healthy CNS, zinc, copper, iron, and manganese play vital roles as enzyme cofactors, supporting neurotransmission, cellular metabolism, and antioxidant defense. Imbalances in these trace elements can lead to oxidative stress, protein aggregation, and mitochondrial dysfunction, thereby contributing to neurodegeneration. In AD, copper and zinc imbalances are associated with amyloid-beta and tau pathology, impacting cognitive function. PD involves the disruption of iron and manganese levels, leading to oxidative damage and neuronal loss. Toxic metals, like lead and cadmium, impair synaptic transmission and exacerbate neuroinflammation, impacting CNS health. The role of aluminum in AD neurofibrillary tangle formation has also been noted. Understanding the roles of these elements in CNS health and disease might offer potential therapeutic targets for neurodegenerative disorders. The Codex Alimentarius standards concerning the mentioned metals in foods may be one of the key legal contributions to safeguarding public health. Further research is needed to fully comprehend these complex mechanisms and develop effective interventions.
Topics: Humans; Parkinson Disease; Copper; Alzheimer Disease; Manganese; Trace Elements; Zinc; Iron; Metals; Neurodegenerative Diseases
PubMed: 37958705
DOI: 10.3390/ijms242115721