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1.
Diagn. tratamento ; 29(2): 67-80, abr-jun. 2024. tab
Article in Portuguese | LILACS, SES-SP | ID: biblio-1553896

ABSTRACT

Contextualização: A suplementação de zinco tem sido recomendada para o tratamento e a prevenção de muitas doenças, mas já foi demonstrado que os achados in vitro não são os mesmos evidenciados na clínica, havendo carência de evidências científicas em humanos, relativa ao real benefício dessa suplementação para o organismo humano. Objetivos: Sumarizar as evidências de revisões sistemáticas da Cochrane, referentes à efetividade da suplementação de zinco para tratamento e prevenção de doenças. Métodos: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca na Cochrane Library (2024), sendo utilizado o descritor "ZINC". Todas as revisões sistemáticas de ensaios clínicos foram incluídas. O desfecho primário de análise foi a melhora clínica, a redução dos sintomas ou a prevenção da doença. Resultados: Quatorze estudos foram incluídos, totalizando 221 ensaios clínicos e 265.113 participantes. Discussão: há evidência de benefício do zinco na anemia falciforme (redução de crises e infecções); na prevenção de diarreia aguda ou persistente em regiões com taxas elevadas de desnutrição; na prevenção da diarreia e melhora no crescimento de crianças de 6 meses a 12 anos de idade; na redução da mortalidade e no ganho de peso a curto prazo em prematuros; e na redução da incidência e prevalência de pneumonia em crianças de 2 a 59 meses de idade. É necessário cautela, pois não há robustez dos resultados e o nível de evidência é limitado. Conclusão: Há evidência de efetividade do zinco em algumas intervenções, mas a evidência é limitada, sugerindo-se a realização de novos estudos prospectivos de qualidade.


Subject(s)
Zinc , Systematic Review , Therapeutics , Clinical Trial , Evidence-Based Practice
2.
J Nutr ; 154(6): 1917-1926, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38621624

ABSTRACT

BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point. RESULTS: At 12-wk gestation and 3-mo postpartum, no statistical differences in mean SZC were observed among arms. At 34-wk, mean SZC for arms 1 and 2 were significantly higher than for arm 3 (50.3, 50.8, 47.8 µg/dL, respectively; P = 0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-wk (<56 µg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 wk (<50 µg/dL), 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-mo postpartum (<66 µg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-wk was associated with lower birth length-for-age Z-scores (all sites P = 0.013, Pakistan P = 0.008) and weight-for-age Z-scores (all sites P = 0.017, Pakistan P = 0.022). CONCLUSIONS: Despite daily zinc supplementation for ≥7 mo, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. This trial is registered at clinicaltrials.gov as #NCT01883193.


Subject(s)
Dietary Supplements , Lactation , Maternal Nutritional Physiological Phenomena , Zinc , Humans , Female , Pregnancy , Zinc/administration & dosage , Zinc/blood , Adult , Infant, Newborn , Prevalence , Young Adult , Pregnancy Complications , India , Nutritional Status , Preconception Care
3.
J Trace Elem Med Biol ; 84: 127450, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38643593

ABSTRACT

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s-1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health.


Subject(s)
Diabetes Mellitus, Experimental , Hemorheology , Rats, Wistar , Zinc , Animals , Zinc/blood , Zinc/pharmacology , Male , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Rats , Hemorheology/drug effects , Blood Glucose/metabolism , Blood Viscosity/drug effects , Disease Models, Animal , Body Weight/drug effects , Dietary Supplements
4.
Analyst ; 149(11): 3161-3168, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38632945

ABSTRACT

This article presents the development of a distance-based thread analytical device (dTAD) integrated with an ion-imprinted polymer (IIP) for quantitative monitoring of zinc ions (Zn2+) in human urine samples. The IIP was easily chemically modified onto the thread channel using dithizone (DTZ) as a ligand to bind to Zn2+ with methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as well as 2,2-azobisisobutyronitrile (AIBN) as cross-linking agents to enhance the selectivity for Zn2+ detection. The imprinted polymer was characterized using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy and Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy (SEM-EDS). Under optimization, the linear detection range was from 1.0 to 20.0 mg L-1 (R2 = 0.9992) with a limit of detection (LOD) of 1.0 mg L-1. Other potentially interfering metal ions and molecules did not interfere with this approach, leading to high selectivity. Furthermore, our technique exhibits a remarkable recovery ranging from 100.48% to 103.16%, with the highest relative standard deviation (% RSD) of 5.44% for monitoring Zn2+ in human control urine samples, indicating high accuracy and precision. Similarly, there is no significant statistical difference between the results obtained using our method and standards on zinc supplement sample labels. The proposed method offers several advantages in detecting trace Zn2+ for point-of-care (POC) medical diagnostics and environmental sample analysis, such as ease of use, instrument-free readout, and cost efficiency. Overall, our developed dTAD-based IIP method holds potential for simple, affordable, and rapid detection of Zn2+ levels and can be applied to other metal ions' analysis.


Subject(s)
Limit of Detection , Zinc , Humans , Zinc/chemistry , Zinc/urine , Molecular Imprinting/methods , Polymers/chemistry , Molecularly Imprinted Polymers/chemistry
5.
Clin Exp Med ; 24(1): 78, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630209

ABSTRACT

Trace elements are essential micronutrients for the human body. Their roles are indispensable, as they are involved in a wide range of vital biological processes. In this study, we aimed to evaluate alterations in trace elements in the blood and bone marrow serum of patients with newly diagnosed multiple myeloma (NMM). The levels of zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), arsenic (As), boron (B), nickel (Ni), silicon (Si) and chromium (Cr) were analyzed in the venous blood samples of the patient group comprising 70 patients with NMM (41 males and 29 females) and compared to those in the control group comprising 30 individuals (18 males and 12 females). In addition, trace element levels were analyzed in bone marrow samples from the patient group. Blood and bone marrow serum levels were quantified using inductively coupled plasma optical emission spectrometry. When the blood samples of the patient and control groups were compared: Zn (p = 0.011), Fe (p = 0.008), Mn (p = 0.046), Se (p < 0.001), As (p < 0.001), Ni (p < 0.001) and Cr (p < 0.001) levels were significantly higher in the patient group than in the control group. Higher Zn, Fe, Mn, Se, As, Ni and Cr levels in the NMM patients suggest that alterations of trace elements could be predisposing factor that initiates the malignant process. The relationship between malignancies and trace elements is crucial for the development of adjuvant therapy strategies and preventive medicine and as biomarkers for cancer diagnosis. Therefore, there is a need for studies examining the relationship between hematological malignancies and trace elements.


Subject(s)
Multiple Myeloma , Trace Elements , Female , Male , Humans , Bone Marrow , Multiple Myeloma/diagnosis , Zinc , Iron
6.
PLoS One ; 19(4): e0300845, 2024.
Article in English | MEDLINE | ID: mdl-38635826

ABSTRACT

Cucurbita moschata (Butternut squash) seeds are a rich source of nutrition containing nutrients including iron, zinc, copper, calcium, potassium, and phosphorus. The aim of this study was to determine if Cucurbita Moschata squash seed paste improves zinc and iron status, anthropometric status, and dietary intake in preschool children. A pretest-posttest control group trial using cluster randomisation was conducted over 6 months. Four preschools were randomly assigned to receive 100 g of intervention or 100 g of a placebo as the control to enhance iron and zinc status. A total of 276 preschool children were recruited from eight government registered Early Childhood Development centres in Limpopo province, South Africa. The control group consumed Cucurbita moschata flesh twice-weekly, while the intervention group consumed Cucurbita moschata seed paste twice-weekly during a six-month period. Iron (serum iron, transferrin, transferrin saturation, ferritin) and zinc (serum zinc) status and anthropometric indices such as weight, height and mid upper arm circumference for children were evaluated at baseline and the endpoint. Iron and zinc-rich food consumption was measured using a 24-hour dietary recall and food record during the study, and dietary intake was estimated using a food frequency questionnaire which was conducted at the beginning and endpoint. The intervention group significantly improved in the mean serum iron 0.23 µg/dL (95% CI: 0.11;0.33); ferritin 0.21µg/dL (95% CI: 0.13;0.39), transferrin saturation 0.33% (0.23;0.74) and zinc 0.16 µmol/dl (95% CI: 0.13;0.25) at the end of the study. In addition, the intervention group exhibited greater mean weight for age of 0.13 z-score (95% CI: 0.28; 0.34) and weight for height of 0.04 z-score (95% CI: 0.12,0.05), as well as the consumption of iron (p < 0,001), zinc (p < 0,001), and vitamin C (p < 0.001). At the end of the trial, fiber (p < 0.001), riboflavin (p = 0.001), vitamin B6 (p < 0.001), and vitamin B12 (p < 0.001) were significantly higher in the control group. Thus, the inclusion of intervention in the diet of children in an impoverished area of South Africa improved the iron and zinc status of these children. This supplement could be a cost effective and sustainable approach to improve nutrient status in rural South Africa. Trial registration: Pan African Clinical Trial Registry (PACTR202308740458863).


Subject(s)
Cucurbita , Iron , Humans , Child, Preschool , Zinc , South Africa , Ferritins , Seeds , Transferrin
7.
Int J Pharm ; 656: 124076, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38569976

ABSTRACT

Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g., PEG antibodies), there is a continual need to develop novel vaccine platforms. Zinc carnosine microparticles (ZnCar MPs), which are composed of a one-dimensional coordination polymer formed between carnosine and the metal ion zinc, have exhibited efficacy in inducing an immune response against influenza. However, ZnCar MPs' limited suspendability hinders clinical application. In this study, we address this issue by mixing mannan, a polysaccharide derived from yeast, with ZnCar MPs. We show that the addition of mannan increases the suspendability of this promising vaccine formulation. Additionally, since mannan is an adjuvant, we illustrate that the addition of mannan increases the antibody response and T cell response when mixed with ZnCar MPs. Mice vaccinated with mannan + OVA/ZnCar MPs had elevated serum IgG and IgG1 levels in comparison to vaccination without mannan. Moreover, in the mannan + OVA/ZnCar MPs vaccinated group, mucosal washes demonstrated increased IgG, IgG1, and IgG2c titers, and antigen recall assays showed enhanced IFN-γ production in response to MHC-I and MHC-II immunodominant peptide restimulation, compared to the vaccination without mannan. These findings suggest that the use of mannan mixed with ZnCar MPs holds potential for subunit vaccination and its improved suspendability further promotes clinical translation.


Subject(s)
Carnosine , Mannans , Vaccines, Subunit , Zinc , Mannans/chemistry , Mannans/administration & dosage , Mannans/immunology , Animals , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology , Zinc/chemistry , Zinc/administration & dosage , Carnosine/administration & dosage , Carnosine/chemistry , Female , Immunoglobulin G/blood , Mice , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/chemistry , Ovalbumin/immunology , Ovalbumin/administration & dosage , Mice, Inbred C57BL , Polymers/chemistry , Polymers/administration & dosage , Mice, Inbred BALB C , Drug Carriers/chemistry
8.
Fish Shellfish Immunol ; 149: 109534, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38575040

ABSTRACT

Zinc is one of the essential microelements for the metabolism of animals. Zinc nanoparticles may have higher bioavailability due to their low specific surface area, facilitating absorption by fish. The present study aimed to evaluate the effects of supplementation with different zinc-based products on the growth and health of Nile tilapia Oreochromis niloticus. Zinc, in different sizes (nanoparticles or bulk) and forms (inorganic or organic), were used as a supplement in the tilapia diet at a dose of 15 mg kg feed-1 for 60 days. At the end of the feeding trial, production performance, hemato-immunological parameters, activity of antioxidant system enzymes, exposure to Streptococcus agalactiae and zinc concentration in the muscle were examined. After the bacterial challenge, the mean corpuscular hemoglobin concentration (MCHC) significantly increased in the fish treated with organic zinc, inorganic nano zinc, and organic nano zinc, while in the control group (inorganic zinc), MCHC remained unchanged. Regarding defense cells, dietary inorganic nano zinc increased the number of basophils (1.50 ± 1.10) compared to organic zinc (0.80 ± 0.90). Lymphocyte count increased after the challenge only in the organic zinc treatments (bulk and nanoparticles). Neutrophils decreased in the control (inorganic zinc) (2.20 ± 1.70) and inorganic nano zinc (2.60 ± 2.70) treatments after the challenge. When compared before and after the bacterial challenge, the plasma antimicrobial titer significantly increased after the bacterial challenge in all treatments. No significant differences were observed for total proteins, enzymes (SOD and CAT), cumulative survival and zinc deposition on fillet. In conclusion, organic zinc in nanoparticles or bulk size increased Nile tilapia innate defense during bacterial infection. However, the other parameters evaluated were not affected by zinc particle size or form (organic or inorganic), indicating that further evaluations should be conducted with organic zinc in nanoparticles or bulk size in the tilapia diet.


Subject(s)
Animal Feed , Cichlids , Diet , Dietary Supplements , Fish Diseases , Streptococcal Infections , Streptococcus agalactiae , Zinc , Animals , Cichlids/immunology , Cichlids/growth & development , Dietary Supplements/analysis , Zinc/administration & dosage , Animal Feed/analysis , Diet/veterinary , Streptococcal Infections/veterinary , Streptococcal Infections/immunology , Streptococcus agalactiae/physiology , Fish Diseases/immunology , Random Allocation , Immunity, Innate/drug effects
9.
Environ Pollut ; 349: 123951, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38604305

ABSTRACT

Phosphorus is one of the important factors to successfully establish the microalgal-bacterial symbiosis (MABS) system. The migration and transformation of phosphorus can occur in various ways, and the effects of phosphate on the MABS system facing environmental impacts like heavy metal stress are often ignored. This study investigated the roles of phosphate on the response of the MABS system to zinc ion (Zn2+). The results showed that the pollutant removal effect in the MABS system was significantly reduced, and microbial growth and activity were inhibited with the presence of Zn2+. When phosphate and Zn2+ coexisted, the inhibition effects of pollutants removal and microbial growth rate were mitigated compared to that of only with the presence of Zn2+, with the increasing rates of 28.3% for total nitrogen removal, 48.9% for chemical oxygen demand removal, 78.3% for chlorophyll-a concentration, and 13.3% for volatile suspended solids concentration. When phosphate was subsequently supplemented in the MABS system after adding Zn2+, both pollutants removal efficiency and microbial growth and activity were not recovered. Thus, the inhibition effect of Zn2+ on the MABS system was irreversible. Further analysis showed that Zn2+ preferentially combined with phosphate could form chemical precipitate, which reduced the fixation of MABS system for Zn2+ through extracellular adsorption and intracellular uptake. Under Zn2+ stress, the succession of microbial communities occurred, and Parachlorella was more tolerant to Zn2+. This study revealed the comprehensive response mechanism of the co-effects of phosphate and Zn2+ on the MABS system, and provided some insights for the MABS system treating wastewater containing heavy metals, as well as migration and transformation of heavy metals in aquatic ecosystems.


Subject(s)
Metals, Heavy , Microalgae , Phosphates , Symbiosis , Wastewater , Water Pollutants, Chemical , Metals, Heavy/metabolism , Wastewater/chemistry , Phosphates/pharmacology , Phosphates/metabolism , Waste Disposal, Fluid/methods , Bacteria/metabolism , Bacteria/drug effects , Zinc
10.
Medicine (Baltimore) ; 103(14): e37741, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579045

ABSTRACT

The gallstone disease is becoming increasingly prevalent worldwide. Dietary trace minerals have been proven to be closely related to many metabolic diseases, and this study aims to explore the association between intakes of dietary trace minerals (copper, iron, selenium, and zinc) and gallstone disease (GSD). Using the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018, intakes of dietary trace minerals and GSD data were obtained through a 24-hour recall and diagnostic questionnaire, respectively. Weighted logistic regression models were used to identify the association between intakes of dietary trace minerals and the prevalence of GSD, and the results were presented as odds ratios (OR) and 95% confidence intervals (95% CI). A total of 4077 participants were included in the final analysis, of which 456 participants had GSD and 3621 participants serving as the control group. No significant associations between GSD and intakes of dietary trace minerals (iron, selenium, and zinc) were found. However, after adjusting for all covariates, significant association was demonstrated between dietary copper (Cu) intake and GSD (OR = 0.66, 95% CI = 0.45-0.98). After conducting a weighted quantile logistic regression, a significant negative correlation was also found between dietary Cu intake and highest GSD quartile (Q4) (OR = 0.45, 95% CI = 0.26-0.80). Following the research outlined above, no association was found between intakes of dietary trace minerals (iron, selenium, and zinc) and GSD; however, a linear negative association was identified between dietary Cu intake and GSD.


Subject(s)
Cholelithiasis , Selenium , Trace Elements , Humans , Nutrition Surveys , Cross-Sectional Studies , Copper , Zinc , Iron
11.
FP Essent ; 539: 13-17, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38648170

ABSTRACT

Micronutrients are nutrients the body needs in small quantities, such as vitamins and minerals. Micronutrient deficiencies can occur when an individual is restricting calorie intake for weight loss or management, not consuming an adequate amount of food to meet energy requirements due to poor appetite or illness, eliminating one or more food groups from the diet on a regular basis, or consuming a diet low in micronutrient-rich foods despite adequate or excessive energy intake. Patient groups at risk include older adults, pregnant patients, patients with alcohol use disorder, patients with vegetarian or vegan diets, and patients with increased requirements secondary to medical conditions or long-term drug use that alters nutrient absorption, metabolism, or excretion. The micronutrients that most commonly require supplementation are vitamin D, iron, vitamin A, zinc, folate, and iodine. Results of large-scale randomized trials have shown no overall benefit of multivitamins for the majority of patients. However, a daily multivitamin may be beneficial, particularly for patients who do not consistently consume a well-balanced diet. Although dietary supplements can be helpful in correcting deficiencies, higher than recommended doses can cause adverse effects. Patients should be advised to take recommended dosages of supplements and consult their physician if they notice any adverse effects. Physicians should advise patients to consult drug labels and/or pharmacists about potential supplement interactions with drugs or other supplements.


Subject(s)
Dietary Supplements , Micronutrients , Humans , Micronutrients/therapeutic use , Vitamins/therapeutic use , Vitamins/administration & dosage , Female , Nutritional Requirements , Pregnancy , Zinc/administration & dosage , Zinc/therapeutic use , Zinc/deficiency
12.
COPD ; 21(1): 2322605, 2024 12.
Article in English | MEDLINE | ID: mdl-38591165

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Copper/therapeutic use , Lung , Oxidative Stress , Iron/therapeutic use , Zinc/therapeutic use
13.
Int J Mol Sci ; 25(7)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38612894

ABSTRACT

With the ambition to identify novel chemical starting points that can be further optimized into small drug-like inhibitors of insulin-regulated aminopeptidase (IRAP) and serve as potential future cognitive enhancers in the clinic, we conducted an ultra-high-throughput screening campaign of a chemically diverse compound library of approximately 400,000 drug-like small molecules. Three biochemical and one biophysical assays were developed to enable large-scale screening and hit triaging. The screening funnel, designed to be compatible with high-density microplates, was established with two enzyme inhibition assays employing either fluorescent or absorbance readouts. As IRAP is a zinc-dependent enzyme, the remaining active compounds were further evaluated in the primary assay, albeit with the addition of zinc ions. Rescreening with zinc confirmed the inhibitory activity for most compounds, emphasizing a zinc-independent mechanism of action. Additionally, target engagement was confirmed using a complementary biophysical thermal shift assay where compounds causing positive/negative thermal shifts were considered genuine binders. Triaging based on biochemical activity, target engagement, and drug-likeness resulted in the selection of 50 qualified hits, of which the IC50 of 32 compounds was below 3.5 µM. Despite hydroxamic acid dominance, diverse chemotypes with biochemical activity and target engagement were discovered, including non-hydroxamic acid compounds. The most potent compound (QHL1) was resynthesized with a confirmed inhibitory IC50 of 320 nM. Amongst these compounds, 20 new compound structure classes were identified, providing many new starting points for the development of unique IRAP inhibitors. Detailed characterization and optimization of lead compounds, considering both hydroxamic acids and other diverse structures, are in progress for further exploration.


Subject(s)
Aminopeptidases , Insulin , High-Throughput Screening Assays , Insulin, Regular, Human , Coloring Agents , Hydroxamic Acids , Zinc
14.
Poult Sci ; 103(6): 103696, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38593549

ABSTRACT

Zinc (Zn) could alleviate the adverse effect of high temperature (HT) on intestinal integrity and barrier function of broilers, but the underlying mechanisms remain unclear. We aimed to investigate the possible protective mechanisms of Zn on primary cultured broiler jejunal epithelial cells exposed to thermal stress (TS). In Exp.1, jejunal epithelial cells were exposed to 40℃ (normal temperature, NT) and 44℃ (HT) for 1, 2, 4, 6, or 8 h. Cells incubated for 8 h had the lowest transepithelial resistance (TEER) and the highest phenol red permeability under HT. In Exp.2, the cells were preincubated with different Zn sources (Zn sulfate as iZn and Zn proteinate with the moderate chelation strength as oZn) and Zn supplemental levels (50 and 100 µmol/L) under NT for 24 h, and then continuously incubated under HT for another 8 h. TS increased phenol red permeability, lactate dehydrogenase (LDH) activity and p-PKC/PKC level, and decreased TEER, cell proliferation, mRNA levels of claudin-1, occludin, zona occludens-1 (ZO-1), PI3K, AKT and mTOR, protein levels of claudin-1, ZO-1 and junctional adhesion molecule-A (JAM-A), and the levels of p-ERK/ERK, p-PI3K/PI3K and p-AKT/AKT. Under HT, oZn was more effective than iZn in increasing TEER, occludin, ZO-1, PI3K, and AKT mRNA levels, ZO-1 protein level, and p-AKT/AKT level; supplementation with 50 µmol Zn/L was more effective than 100 µmol Zn/L in increasing cell proliferation, JAM-A, PI3K, AKT, and PKC mRNA levels, JAM-A protein level, and the levels of p-ERK/ERK and p-PI3K/PI3K; furthermore, supplementation with 50 µmol Zn/L as oZn had the lowest LDH activity, and the highest ERK, JNK-1, and mTOR mRNA levels. Therefore, supplemental Zn, especially 50 µmol Zn/L as oZn, could alleviate the TS-induced integrity and barrier function damage of broiler jejunal epithelial cells possibly by promoting cell proliferation and tight junction protein expression via the MAPK and PI3K/AKT/mTOR signaling pathways.


Subject(s)
Epithelial Cells , Jejunum , Phosphatidylinositol 3-Kinases , Signal Transduction , TOR Serine-Threonine Kinases , Animals , Jejunum/drug effects , Epithelial Cells/drug effects , Signal Transduction/drug effects , Chick Embryo , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Zinc/administration & dosage , Zinc/pharmacology , Chickens , Avian Proteins/metabolism , Avian Proteins/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Cells, Cultured , Heat-Shock Response/drug effects , Hot Temperature/adverse effects , MAP Kinase Signaling System/drug effects
15.
Commun Biol ; 7(1): 432, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594418

ABSTRACT

Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.


Subject(s)
Selenium , Trace Elements , Male , Humans , Trace Elements/metabolism , Genome-Wide Association Study , Zinc , Selenium/analysis , Manganese
16.
Int J Mol Sci ; 25(7)2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38612424

ABSTRACT

This work is aimed at relationships which govern zinc and copper uptake by four popular medicinal herbs: basil (Ocimum basilicum L.), borage (Borago officinalis L.), common nettle (Urtica dioica L.) and peppermint (Mentha piperita L.). They are often grown in soils with significant copper or zinc levels. Herbs were cultivated by a pot method in controlled conditions. Manganese, iron, copper and zinc concentrations were determined by High-Resolution Continuum Source Flame Atomic Absorption Spectrometry. The efficiency of photosynthesis was estimated by measuring the chlorophyll content, water use efficiency, net photosynthesis, intercellular CO2, stomatal conductance, and transpiration rate. Phenolic compounds were determined by the Folin-Ciocalteu method. Analysis of variance showed that herbs grown in soil treated with copper exhibited a lower iron content in roots, while manganese behaved in the opposite way. The only exception was borage, where a decrease in the manganese content in roots was observed. Both copper and zinc supplementations increased the total content of phenolics, while the highest increases were observed for common nettle and basil. Peppermint and borage responded less to supplementation. In the majority of samples, zinc and copper did not significantly affect the photosynthesis. Herbal extracts from common nettle and basil had unique antioxidant properties and may be good free radical scavengers.


Subject(s)
Borago , Ocimum basilicum , Urtica dioica , Mentha piperita , Copper , Zinc , Manganese , Phenols , Photosynthesis , Iron
17.
Int J Mol Sci ; 25(7)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38612631

ABSTRACT

Trace elements are essential for maintaining the body's homeostasis, and their special role has been demonstrated in skin physiology. Among the most important trace elements are zinc, copper, and iron. A deficiency or excess of trace elements can be associated with an increased risk of skin diseases, so increasing their supplementation or limiting intake can be helpful in dermatological treatment. In addition, determinations of their levels in various types of biological material can be useful as additional tests in dermatological treatment. This paper describes the role of these elements in skin physiology and summarizes data on zinc, copper, and iron in the course of selected, following skin diseases: psoriasis, pemphigus vulgaris, atopic dermatitis, acne vulgaris and seborrheic dermatitis. In addition, this work identifies the potential of trace elements as auxiliary tests in dermatology. According to preliminary studies, abnormal levels of zinc, copper, and iron are observed in many skin diseases and their determinations in serum or hair can be used as auxiliary and prognostic tests in the course of various dermatoses. However, since data for some conditions are conflicting, clearly defining the potential of trace elements as auxiliary tests or elements requiring restriction/supplement requires further research.


Subject(s)
Acne Vulgaris , Trace Elements , Humans , Zinc , Copper , Iron
18.
Sci Rep ; 14(1): 8590, 2024 04 13.
Article in English | MEDLINE | ID: mdl-38615144

ABSTRACT

Hypertension (HPT) is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. Currently, attention is given to various dietary approaches with a special focus on the role of micronutrient intake in the regulation of blood pressure. This study aims to measure the dietary intake of selected minerals among Malaysian adults and its association with HPT. This cross-sectional study involved 10,031 participants from the Prospective Urban and Rural Epidemiological study conducted in Malaysia. Participants were grouped into HPT if they reported having been diagnosed with high blood pressure [average systolic blood pressure (SBP)/average diastolic blood pressure (DBP) ≥ 140/90 mm Hg]. A validated food frequency questionnaire (FFQ) was used to measure participants' habitual dietary intake. The dietary mineral intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc was measured. The chi-square test was used to assess differences in socio-demographic factors between HPT and non-HPT groups, while the Mann-Whitney U test was used to assess differences in dietary mineral intake between the groups. The participants' average dietary intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, selenium, sodium, and zinc was 591.0 mg/day, 3.8 mg/day, 27.1 mg/day, 32.4 mg/day, 0.4 mg/day, 1431.1 mg/day, 2.3 g/day, 27.1 µg/day, 4526.7 mg/day and 1.5 mg/day, respectively. The intake was significantly lower among those with HPT than those without HPT except for calcium and manganese. Continuous education and intervention should be focused on decreasing sodium intake and increasing potassium, magnesium, manganese, zinc, and calcium intake for the general Malaysian population, particularly for the HPT patients.


Subject(s)
Hypertension , Selenium , Adult , Humans , Cross-Sectional Studies , Calcium , Manganese , Copper , Magnesium , Prospective Studies , Hypertension/epidemiology , Calcium, Dietary , Iron , Zinc , Sodium , Phosphorus , Potassium
19.
BMC Pediatr ; 24(1): 251, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605385

ABSTRACT

BACKGROUND: Dilated cardiomyopathy (DCMP) is characterized by the enlargement and weakening of the heart and is a major cause of heart failure in children. Infection and nutritional deficiencies are culprits for DCMP. Zinc is an important nutrient for human health due to its anti-oxidant effect that protects cell against oxidative damage. This case-control study aimed to investigate the relationship between dietary intake of zinc and selenium and the risk of DCMP in pediatric patients. METHODS: A total of 36 DCMP patients and 72 matched controls were recruited, and their dietary intakes were assessed via a validated food frequency questionnaire. We used chi-square and sample T-test for qualitative and quantitative variables, respectively. Logistic regression analysis was applied to assess the relationship between selenium and zinc intake with the risk of DCMP. RESULTS: After fully adjusting for confounding factors, analyses showed that selenium (OR = 0.19, CI = 0.057-0.069, P trend < 0.011) and zinc (OR = 0.12, CI = 0.035-0.046, P trend < 0.002) intake were strongly associated with 81% and 88% lower risk of pediatric DCMP, respectively. CONCLUSIONS: This study highlights the protective role of adequate dietary intake of selenium and zinc in decreasing the risk of DCMP in children. Malnutrition may exacerbate the condition and addressing these micronutrient deficiencies may improve the cardiac function. Further studies are recommended to detect the underlying mechanisms and dietary recommendations for DCMP prevention.


Subject(s)
Cardiomyopathy, Dilated , Malnutrition , Selenium , Humans , Child , Selenium/analysis , Case-Control Studies , Cardiomyopathy, Dilated/etiology , Deoxycytidine Monophosphate , Zinc , Malnutrition/complications
20.
Nat Commun ; 15(1): 3167, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609367

ABSTRACT

Heme has a critical role in the chemical framework of the cell as an essential protein cofactor and signaling molecule that controls diverse processes and molecular interactions. Using a phylogenomics-based approach and complementary structural techniques, we identify a family of dimeric hemoproteins comprising a domain of unknown function DUF2470. The heme iron is axially coordinated by two zinc-bound histidine residues, forming a distinct two-fold symmetric zinc-histidine-iron-histidine-zinc site. Together with structure-guided in vitro and in vivo experiments, we further demonstrate the existence of a functional link between heme binding by Dri1 (Domain related to iron 1, formerly ssr1698) and post-translational regulation of succinate dehydrogenase in the cyanobacterium Synechocystis, suggesting an iron-dependent regulatory link between photosynthesis and respiration. Given the ubiquity of proteins containing homologous domains and connections to heme metabolism across eukaryotes and prokaryotes, we propose that DRI (Domain Related to Iron; formerly DUF2470) functions at the molecular level as a heme-dependent regulatory domain.


Subject(s)
Hemeproteins , Synechocystis , Heme , Zinc , Histidine , Hemeproteins/genetics , Synechocystis/genetics , Carbon , Iron
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