Copper Deficiency Research Articles

Intelligent gold nanocluster for effective treatment of malignant tumor via tumor-specific photothermal-chemodynamic therapy with AIE guidance.

Precise and efficient therapy of malignant tumors is always a challenge. Herein, gold nanoclusters co-modified by aggregation-induced-emission (AIE) molecules, copper ion chelator (acylthiourea) and tumor-targeting agent (folic acid) were fabricated to perform AIE-guided and tumor-specific synergistic therapy with great spatio-temporal controllability for the targeted elimination and metastasis inhibition of malignant tumors. During therapy, the functional gold nanoclusters (AuNTF) would rapidly accumulate in the tumor tissue due to the enhanced permeability and retention effect as well as folic acid-mediated tumor targeting, which was followed by endocytosis by tumor cells. After that, the overexpressed copper ions in the tumor cells would trigger the aggregation of these intracellular AuNTF via a chelation process that not only generated the photothermal agent in situ to perform the tumor-specific photothermal therapy damaging the primary tumor, but also led to the copper deficiency of tumor cells to inhibit its metastasis. Moreover, the copper ions were reduced to cuprous ions along with the chelation, which further catalysed the excess H2O2 in the tumor cells to produce cytotoxic reactive oxygen species, resulting in additional chemodynamic therapy for enhanced antitumor efficiency. The aggregation of AuNTF also activated the AIE molecules to present fluorescence, which not only imaged the therapeutic area for real-time monitoring of this tumor-specific synergistic therapy, but also allowed us to perform near-infrared radiation at the correct time point and location to achieve optimal photothermal therapy. Both in vitro and in vivo results revealed the strong tumor elimination, effective metastasis inhibition and high survival rate of tumor-bearing mice after treatment using the AuNTF nanoclusters, indicating that this AIE-guided and tumor-specific synergistic strategy could offer a promising approach for tumor therapy.

Green solution to riparian pollution: Populus alba L. potential for phytoremediation and bioindication of PTEs along the Sava river

This study addresses the potential of Populus alba L. for bioindication and phytoremediation of the contaminated lower part of the Sava River. The main objectives are to assess soil contamination with potentially toxic elements (PTEs: As, B, Cd, Cr, Cu, Li, Ni, Pb, Sr, and Zn), evaluate their availability, and assess the phytoremediation and bioindication potential of Populus alba. Quantification of the PTE contents was performed using inductively coupled plasma optical emission spectroscopy (ICP-OES), while bioindication and phytoremediation potential were evaluated using accumulation indices. The study revealed phytotoxic contents of Cr, Cu, Ni and Zn in the riparian soils of the lower Sava River. The percentage of available Cd was high, but due to its low total content, its phytotoxic potential is limited. According the metal accumulation index, Populus alba exhibits significant potential to accumulate the PTEs studied (with accumulated toxic contents of B, Cr, Li, Sr, and Zn). The ability of Populus alba to accumulate and bioindicate Cd, Cr, and Ni is promising, as is its ability to potentially remediate B, Cd, and Zn. Copper deficiency in leaves resulted in a reduction in photosynthetic performance, but without visible morphological symptoms. The reduced photosynthetic capacity serves as an adaptive strategy for this species in response to toxic levels of PTEs. Since Populus alba is widely distributed in European riparian forests, it is a good candidate to address soil contamination through phytoremediation and bioindication techniques.

Potential cellular targets of platinum in the freshwater microalgae Chlamydomonas reinhardtii and Nitzschia palea revealed by transcriptomics.

Platinum group element levels have increased in natural aquatic environments in the last few decades, in particular as a consequence of the use of automobile catalytic converters on a global scale. Concentrations of Pt over tens of μg L-1 have been observed in rivers and effluents. This raises questions regarding its possible impacts on aquatic ecosystems, as Pt natural background concentrations are extremely low to undetectable. Primary producers, such as microalgae, are of great ecological importance, as they are at the base of the food web. The purpose of this work was to better understand the impact of Pt on a cellular level for freshwater unicellular algae. Two species with different characteristics, a green alga C. reinhardtii and a diatom N. palea, were studied. The bioaccumulation of Pt as well as its effect on growth were quantified. Moreover, the induction or repression factors of 16 specific genes were determined and allowed for the determination of possible intracellular effects and pathways of Pt. Both species seemed to be experiencing copper deficiency as suggested by inductions of genes linked to copper transporters. This is an indication that Pt might be internalized through the Cu(I) metabolic pathway. Moreover, Pt could possibly be excreted using an efflux pump. Other highlights include a concentration-dependent negative impact of Pt on mitochondrial metabolism for C. reinhardtii which is not observed for N. palea. These findings allowed for a better understanding of some of the possible impacts of Pt on freshwater primary producers, and also lay the foundations for the investigation of pathways for Pt entry at the base of the aquatic food web.

Distinct function of Chlamydomonas CTRA-CTR transporters in Cu assimilation and intracellular mobilization.

Regulation of Cu uptake and sequestration by members of the CTR family of proteins in Chlamydomonas.

APX2 Is an Ascorbate Peroxidase-Related Protein that Regulates the Levels of Plastocyanin in Chlamydomonas.

The function of ascorbate peroxidase-related (APX-R) proteins, present in all green photosynthetic eukaryotes, remains unclear. This study focuses on APX-R from Chlamydomonas reinhardtii, namely, ascorbate peroxidase 2 (APX2). We showed that apx2 mutants exhibited a faster oxidation of the photosystem I primary electron donor, P700, upon sudden light increase and a slower re-reduction rate compared to the wild type, pointing to a limitation of plastocyanin. Spectroscopic, proteomic and immunoblot analyses confirmed that the phenotype was a result of lower levels of plastocyanin in the apx2 mutants. The redox state of P700 did not differ between wild type and apx2 mutants when the loss of function in plastocyanin was nutritionally complemented by growing apx2 mutants under copper deficiency. In this case, cytochrome c6 functionally replaces plastocyanin, confirming that lower levels of plastocyanin were the primary defect caused by the absence of APX2. Overall, the results presented here shed light on an unexpected regulation of plastocyanin level under copper-replete conditions, induced by APX2 in Chlamydomonas.

Maternal dietary copper deficiency induces cardiomyopathy and liver injury in mice by activating autophagy

Maternal nutritional deficiencies during pregnancy result in birth defects and elevate the risk of cardiovascular diseases and metabolic diseases. Accumulating evidence suggests that deficiency of copper, a fundamental trace element involved in several pivotal physiological processes, promotes the onset of multiple diseases, notably heart and liver diseases. Yet, exploration into the effects of maternal copper deficiency (CuD) on offspring is still limited. In this study, we hypothesized that maternal CuD induced cardiomyopathy and liver injury in offspring through the activation of autophagy. We established a maternal CuD mouse model by feeding pregnant C57BL/6 mice with a CuD diet until the end of the experiment. Echocardiography, histological analysis, western blotting, and quantitative polymerase chain reaction were performed on offspring at postnatal day 14. We found that maternal CuD caused growth retardation and early postnatal death in the offspring. Furthermore, our results revealed that CuD induced cardiac systolic dysfunction, cardiac hypertrophy, hepatic steatosis, and liver injury. Moreover, higher expression of LC3 and lower expression of p62 were observed in the heart tissues and liver tissues of CuD mice compared with the control group, indicating that CuD induced autophagy activation. In conclusion, maternal CuD caused severely deleterious effects on the heart and liver of the offspring via activating autophagy.

Post-marketing surveillance of zinc acetate dihydrate for hypozincemia in Japan.

Zinc is an essential microelement, and its deficit causes various diseases and symptoms. In adults, especially in elderly individuals, zinc shortage can cause symptoms such as taste disorder, dermatitis, and susceptibility to infection. In children, zinc deficiency can lead to growth retardation. In 2017, the indication for zinc acetate dihydrate (NOBELZIN®) was expanded from Wilson's disease to include hypozincemia, leading to wider use of zinc acetate dihydrate. At five years after this broadening of use, we conducted a post-marketing study (PMS) to investigate the utilization, safety, and effectiveness of zinc acetate dihydrate. Over 52 weeks, the overall incidence of adverse drug reactions (ADRs) was 9.4% (87/928). The most common ADR was copper deficiency (2.4%), followed by nausea (1.4%). Among 928 patients, 19 (2%) developed serious ADRs. Of the patients with copper deficiency, 92% were >65 years of age, and all had comorbidities at baseline. Physicians evaluated the effectiveness of zinc acetate dihydrate using three categories: "effective", "not effective", and "indeterminate". The overall efficacy rate was 83.0%. The average serum zinc levels were elevated from 50-60 μg/dL to >90 μg/dL within 12 weeks, and were maintained up to 52 weeks after administration. Among the symptomatic sub-categories, the efficacy rate was highest in pressure ulcer (96.2%; 25/26), followed by in stomatitis (87.5%; 42/48), and taste disorder (87.4%; 181/207). Among pediatric patients with developmental symptoms, an efficacy rate of 66% was achieved. In conclusion, zinc acetate dihydrate has been safely used, and has produced beneficial effects on various diseases and symptoms.

Transcriptomics and metabolomics analysis reveal the dietary copper deficiency and supplementation effects of liver gene expression and metabolite change in grazing sheep.

The appropriate mineral nutrients are essential for sheep growth and reproduction. However, traditional grazing sheep often experience mineral nutrient deficiencies, especially copper (Cu), due to inadequate mineral nutrients from natural pastures. The results indicated that dietary Cu deficiency and supplementation significantly reduced and elevated liver concentration of Cu, respectively (p < 0.05). FOXO3, PLIN1, ACTN2, and GHRHR were identified as critical genes using the weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR), and receiver operating characteristic curve (ROC) validation as potential biomarkers for evaluating Cu status in grazing sheep. Combining these critical genes with gene functional enrichment analysis, it was observed that dietary Cu deficiency may impair liver regeneration and compromise ribosomal function. Conversely, dietary Cu supplementation may enhance ribosomal function, promote lipid accumulation, and stimulate growth and metabolism in grazing sheep. Metabolomics analysis indicated that dietary Cu deficiency significantly decreased the abundance of metabolites such as cholic acid (p < 0.05). On the other hand, dietary Cu supplementation significantly increased the abundance of metabolites such as palmitic acid (p < 0.05). Integrative analysis of the transcriptome and metabolome revealed that dietary Cu deficiency may reduce liver lipid metabolism while Cu supplementation may elevate it in grazing sheep. The Cu content in diets may have an impact on hepatic lipid metabolism in grazing sheep. These findings provide new insights into the consequences of dietary Cu deficiency and supplementation on sheep liver and can provide valuable guidance for herders to rationalize the use of mineral supplements.

Current understanding of essential trace elements in intrahepatic cholestasis of pregnancy.

Trace elements are important components in the body and have fundamental roles in maintaining a healthy and balanced pregnancy process.Either deficiency or excess of trace elements, including selenium, iron, zinc, copper, and magnesium can lead to pregnancy complications. As a rare disorder during pregnancy of unknown aetiology, intrahepatic cholestasis of pregnancy (ICP) poses a significant risk to the fetus of perinatal mortality. ICP is a multifactorial complication of which the pathogenesis is still an enigma. Epidemiological studies have demonstrated the association of ICP with some trace elements. Evidence from retrospective studies in humans further revealed the possible contributing roles of trace elements in the pathogenesis of ICP. The published literature on the association of trace elements with ICP was reviewed. Recent advances in molecular biological techniques from animal studies have helped to elucidate the possible mechanisms by how these trace elements function in regulating oxidative reactions, inflammatory reactions and immune balance in the maternal-fetal interface, as well as the influence on hepato-intestinal circulation of bile acid. The scenario regarding the role of trace elements in the pathogenesis of ICP is still developing. The administration or depletion of these trace elements may have promising effects in alleviating the symptoms and improving the pregnancy outcomes of ICP.

Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases.

Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Exploring metabolic responses and pathway changes in CHO-K1 cells under varied aeration conditions and copper supplementations using 1 H NMR-based metabolomics.

The optimization of bioprocess for CHO cell culture involves careful consideration of factors such as nutrient consumption, metabolic byproduct accumulation, cell growth, and monoclonal antibody (mAb) production. Valuable insights can be obtained by understanding cellular physiology to ensure robust and efficient bioprocess. This study aims to improve our understanding of the CHO-K1 cell metabolism using 1 H NMR-based metabolomics. Initially, the variations in culture performance and metabolic profiles under varied aeration conditions and copper supplementations were thoroughly examined. Furthermore, a comprehensive metabolic pathway analysis was performed to assess the impact of these conditions on the implicated pathways. The results revealed substantial alterations in the pyruvate metabolism, histidine metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis, which were especially evident in cultures subjected to copper deficiency conditions. Conclusively, significant metabolites governing cell growth and mAb titer were identified through orthogonal partial least square-discriminant analysis (OPLS-DA). Metabolites, including glycerol, alanine, formate, glutamate, phenylalanine, and valine, exhibited strong associations with distinct cell growth phases. Additionally, glycerol, acetate, lactate, formate, glycine, histidine, and aspartate emerged as metabolites influencing cell productivity. This study demonstrates the potential of employing 1 H NMR-based metabolomics technology in bioprocess research. It provides valuable guidance for feed medium development, feeding strategy design, bioprocess parameter adjustments, and ultimately the enhancement of cell proliferation and mAb yield.

High-iron consumption decreases copper accumulation and colon length, and alters serum lipids

In this study, we aimed to demonstrate that a significant increase in dietary iron intake disrupts the regulation of copper availability, ultimately leading to systemic copper deficiency. To investigate this, we conducted experiments using five-week-old male weanling Sprague–Dawley rats fed diets based on AIN-93G with some modifications. These diets featured varying iron content, offering choices of adequate iron (~ 120 μg/g, near the upper limit [UL]) or high iron (~ 7544 μg/g), along with low (~ 0.3 μg/g), adequate (~ 6 μg/g), or high (~ 153 μg/g) levels of dietary copper over a 5-week period. Rats consuming the high-iron diets displayed anemia, reduced copper levels in their organs and feces, and shortened colon lengths. Increased dietary iron intake resulted in an overall reduction in copper distribution within the body, likely leading to severe copper deficiency-related disorders in the experimental rats. However, the physiological disturbances caused by a high-iron diet were prevented when additional copper was included in the rodent diet. Furthermore, high iron intake led to copper deprivation, and high iron consumption resulted in elevated serum cholesterol levels. However, increasing dietary copper consumption led to a decrease in overall serum cholesterol levels. Additionally, serum alkaline phosphate and aspartate aminotransferase levels were increased by high-iron feeding, regardless of dietary copper concentration, while alanine aminotransferase levels decreased.

Fructose aggravates copper-deficiency-induced cardiac remodeling by inhibiting SERCA2a.

Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling. We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed. Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration. Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.

P937 A Retropective Analysis of Micronutrient Status in Inflammatory Bowel Disease

Abstract Background Researchers are increasingly focusing on the influence of micronutrient levels on the initiation and prognosis of Inflammatory Bowel Disease (IBD). Earlier investigations have highlighted a connection between deficiencies in zinc and selenium and an elevated risk of IBD development and unfavorable outcomes. This study seeks to investigate the existing micronutrient status among Chinese patients with IBD and assess whether deficiencies in trace elements are associated with disease activity, extent of intestinal involvement, and the use of biological treatments. Methods This cross-sectional study included patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) who underwent plasma micronutrient testing during outpatient or inpatient visits to the Department of Gastroenterology at Peking Union Medical College Hospital from May 2022 to October 2023. Baseline data, the history of biological agent use, and laboratory inflammation parameters such as hsCRP, ESR, and Alb were extracted from the Electronic Medical Record System. Colonoscopy images were examined to assess the extent of intestinal involvement and endoscopic activity. The distribution of micronutrient deficiency among patients with varying disease statuses was explored using the Pearson chi-square test and Mann-Whitney U-test. Results Among the 168 participants with IBD in this study (77 with CD, 91 with UC), a frequent occurrence of deficiencies in copper, selenium, strontium, and zinc was noted. In CD patients in the endoscopic active phase, there was a higher incidence of selenium and zinc deficiencies compared to the remission phase (selenium 0% vs. 11.3%, p=0.17; zinc 4.2% vs. 24.5%, p=0.052). In UC patients during the endoscopic active phase, strontium (14.5% vs. 0%, p=0.053) and zinc (17.7% vs. 3.4%, p=0.094) deficiencies were more likely to occur. CD patients with zinc deficiency and UC patients lacking zinc or selenium showed higher levels of blood hsCRP and ESR but lower levels of serum albumin. UC patients with E3 type involvement were more prone to selenium and strontium deficiencies compared to those with only left colon involvement (selenium 18.5% vs. 2.7%, p=0.025; strontium 14.8% vs. 5.0%, p=0.078). Conclusion This study identified a notable prevalence of micronutrient deficiencies in individuals with IBD, particularly during active phases. Specifically, patients with CD in an inflammatory state are inclined to exhibit zinc deficiency. In the case of UC, the absence of selenium, strontium, and zinc signals a higher level of inflammation. UC patients with involvement of the entire colon are more prone to experiencing deficiencies in selenium and strontium. These findings warrant validation through multi-center study and mechanism invetigation.

Effects of dietary minerals deficiency and supplementation on different parts of muscle minerals content in grazing Mongolian sheep.

The objective of this study was to investigate the impact of dietary deficiency and supplementation of calcium, zinc, copper, cobalt, manganese or selenium on minerals content in the longissimus dorsi (LD), biceps femoris (BF) and triceps brachii (TB) of grazing Mongolian sheep. We randomly divided 98 sheep into 7 treatment groups and fed them specific diets for 60 days: a total mineral nutrition diet (LCG), a calcium deficiency diet (LCa), a zinc deficiency diet (LZn), a copper deficiency diet (LCu), a cobalt deficiency diet (LCo), a manganese deficiency diet (LMn) and a selenium deficiency diet (LSe). Then 7 sheep from each group were slaughtered and samples of LD, BF and TB were collected for mineral content analysis. The remaining sheep in each group were subsequently fed specific diets for an additional 41 days: a total mineral nutrition diet (SCG), a calcium supplementation diet (SCa), a zinc supplementation diet (SZn), a copper supplementation diet (SCu), a cobalt supplementation diet (SCo), a manganese supplementation diet (SMn) and a selenium supplementation diet (SSe). Afterward, all sheep were slaughtered, and muscle samples were collected and analyzed. Significant findings emerged that LCa decreased sulfur (S) content in BF and increased Ca content in LD and BF, while SCa increased S and Ca content in BF and TB, respectively (P < 0.05). LZn decreased Zn, S, and potassium (K) content in LD and BF, while SZn increased Zn and S content in LD and BF, respectively (P < 0.05). LCu decreased Cu and iron (Fe) content in LD and TB, while SCu increased Fe content in TB (P < 0.05). LCo decreased phosphorus, S, K, Ca, Mn, Fe, Cu, and Zn content in LD (P < 0.05). LMn decreased Mn content and increased K content in TB, while SMn decreased K content in BF and TB (P < 0.05). LSe and SSe decreased and increased Se content in LD, BF, and TB, respectively (P < 0.05). Dietary mineral levels have varying effects on lamb meat minerals content. It is important to ensure an adequate intake of minerals in the diet to enhance the mineral nutrition of lamb meat.

Enterosorbent from modified glauconite concentrate in the feeding of young cattle

Currently, the fi rst place is taken by the qualities of feed additives used in feeding highly productive cattle, such as biological and sorption activity, harmlessness and bioavailability. For this reason, recently there has been a significant increase in scientific and practical interest in the use of feed additives that help not only increase the productivity of farm animals, but also improve their health. The purpose of the work was to study enterosorbent from a modifi ed glauconite concentrate in feeding young cattle. A study of glauconite from the Bondar deposit in the Tambov region as a feed additive in the ratrions of young cattle was carried out. New knowledge has been obtained about the sorption properties of this mineral, its eff ect on the absorption and excretion of various metals from the body of animals, including micro- and macronutrients, as well as metal pollutants. Safe eff ective doses of its introduction into animal rations have been determined. It was experimentally fed to older replacement young animals as part of a mono feed. It has been established that the use of enterosorbent based on a modifi ed glauconite concentrate in the ration of young cattle at a dose of 0,2 g/kg of live weight helped to remove nickel from the body of animals up to 60 %, and lead up to 36 % of the total amount, which on average was excreted in feces. The sorbent showed average effi ciency in relation to copper approximately 13 % of its amount is bound and excreted in feces. In this case, the mineral accumulated in the digestive tract of animals for 3–4 days. Under conditions of copper defi ciency in feed, sorbent retention promoted better absorption of inorganic forms of this nutrient consumed with mineral additives.

Effect of water sulfate and dietary bismuth subsalicylate on feed and water intake, ruminal hydrogen sulfide concentration, and trace-mineral status of growing beef heifers.

In the Northern Great Plains, cattle may be exposed to water with an elevated sulfate concentration resulting in ruminal hydrogen sulfide (H2S) production and risk of copper deficiency. There are currently few strategies available to help mitigate effects arising from high-sulfate water (HS). The objective of this study was to evaluate the effects of feeding a moderate-forage diet with or without bismuth subsalicylate (BSS; 0.0% vs. 0.4% DM basis) when provided water with a low- (LS; 346 ± 13) or HS (4,778 ± 263mg/L) concentration on feed and water intake, ruminal H2S concentration, and liver and serum trace-mineral concentrations. Twenty-four Limousin × Simmental cross beef heifers (221 ± 41kg) were stratified based on initial liver Cu into a completely randomized block design with a 2 × 2 factorial treatment arrangement. Feed and water intake (measured weekly), ruminal H2S concentration (measured on days 42 and 91), liver (measured on days -13 and 91), and serum trace-mineral concentrations (measured on days 1, 28, 56, and 91) were evaluated. Initial liver trace-mineral concentrations were used as a covariate in the statistical model. Water intake tended to be reduced with the inclusion of BSS (P = 0.095) but was not affected by water sulfate (P = 0.40). Water sulfate and BSS did not affect dry matter intake (DMI; P ≥ 0.89). Heifers consuming HS had a ruminal H2S concentration that was 1.58mg/L more (P < 0.001) than LS. The inclusion of BSS reduced (P = 0.035) ruminal H2S concentration by more than 44% (1.35 vs. 0.75mg/L). Regardless of the water sulfate concentration, heifers fed BSS had lesser liver Cu concentration (average of 4.08mg/kg) than heifers not provided BSS, and when not provided BSS, HS had lesser Cu than LS (42.2 vs. 58.3; sulfate × BSS, P = 0.019). The serum concentration of Cu did not differ over time for heifers not provided BSS; whereas, heifers provided BSS had lesser serum Cu concentration on day 91 than on days 28 and 55 (BSS × time, P < 0.001). The liver concentration of selenium was reduced (P < 0.001) with BSS inclusion but the selenium concentration in serum was not affected by sulfate, BSS, or time (P ≥ 0.16). BSS reduced ruminal H2S concentration, but depleted liver Cu and Se. Moreover, sulfate concentration in water did not appear to affect DMI, water intake, or growth, but increased ruminal H2S and reduced liver Cu concentration.

Copper release by MOF-74(Cu): a novel pharmacological alternative to diseases with deficiency of a vital oligoelement.

Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.

Discussion of the biochemical mechanisms of copper deficiency in Karakul sheep bred in the Hungry Steppe and its prevention

Based on the literature data and the results of our own research, the article provides a detailed discussion of the mechanisms of occurrence, development and deepening of copper metabolism in Karakul sheep grazing in the biogeochemical province of the Hungry Steppe of the Republic of Uzbekistan. Studies have established correlations between the copper content in the liver and blood, between the copper content in the blood and the activity of copper-containing blood enzymes, between the copper content in the blood and the activity of copper-containing liver enzymes, between the activity of copper-containing enzymes in the blood and liver. Based on the use of these correlations, a convenient test has been developed, using which it is possible to establish the supply of the organism of Karakul sheep with copper, bred in the conditions of the Hungry Steppe. As a result of testing this test technique, a flock of sheep of 465 heads was examined and 76 (16.34%) heads with copper deficiency were identified, of which 8 (1.72%) had clear signs of endemic ataxia. Subsequently, these animals were fed with copper sulfate in the form of a salt mixture mixed with table salt, and their complete recovery was achieved.

Pathophysiology of sideroblastic anemia

Sideroblastic anemias (SAs) are a diverse group of congenital and acquired disorders, characterized by anemia and the presence of ring sideroblasts in bone marrow. Congenital SA is a rare disorder that results from genetic mutations that impair heme biosynthesis, iron-sulfur [Fe-S] cluster biosynthesis, and mitochondrial protein synthesis. The predominant type of congenital SA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific δ-aminolevulinate synthase (ALAS2) gene, a key enzyme in the heme biosynthesis pathway in erythroid cells. SAs can also arise due to exposure to certain drugs or alcohol or to copper deficiency (secondary SAs). They are also often associated with myelodysplastic syndrome (idiopathic SA), and idiopathic SAs are the most frequently encountered type. This review discusses the current understanding of the pathophysiology underlying SA.