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Background: Skin aging is a multifactorial phenomenon which causes alterations in skin physiological functions and, most visibly, phenotypic changes. In particular, during the aging process, hyaluronic acid, collagen, and elastin fibers undergo structural and functional changes. Aims: This study aimed to give an insight into the photo-protective benefits and efficacy of an oral liquid nutricosmeceutical containing collagen bioactive peptides and antioxidants to counteract the signs of aging. Methods: A double-blind, randomized, placebo-controlled clinical trial was conducted by an independent esthetic clinic on 120 healthy volunteer subjects for 90 days. Subjects were divided into 2 groups: 60 subjects consumed 1 bottle (50 mL) of the nutricosmeceutical daily and the other 60 consumed 1 bottle (50 mL) of the placebo. Outcome measures were related to skin elasticity (expressed as Young's elasticity modulus) and skin architecture (histological analysis). In addition, the subjects recruited in this study underwent observational assessments through self-assessment questionnaires. Results and Conclusions: Overall, we demonstrated a significant increase in skin elasticity (+7.5%), p ≤ 0.001 and an improvement in skin texture after daily oral consumption of the nutricosmeceutical. We also obtained a positive patient feedback through the self-assessment questionnaires. Taken together these results show that this nutricosmeceutical supplement may have photo-protective effects and help improve skin health.

To evaluate 3 formulations of copper (Cu)-based self-sanitizing surfaces for antimicrobial efficacy and durability over 1 year in inpatient clinical areas and laboratories. Randomized control trial. We assessed 3 copper formulations: (1) solid alloy 80% Cu-20% Ni (integral copper), (2) spray-on 80% Cu-20% Ni (spray-on) and (3) 16% composite copper-impregnated surface (CIS). In total, 480 coupons (1 cm2) of the 3 products and control surgical grade (AISI 316) stainless steel were inserted into gaskets and affixed to clinical carts used in patient care areas (including emergency and maternity units) and on microbiology laboratory bench work spaces (n = 240). The microbial burden and assessment of resistance to wear, corrosion, and material compatibility were determined every 3 months. Participants included 3 tertiary-care Canadian adult hospital and 1 pediatric-maternity hospital. Copper formulations used on inpatient units statistically significantly reduced bacterial bioburden compared to stainless steel at months 3 and 6. Only the integral copper product had significantly less bacteria than stainless steel at month 12. No statistically significant differences were detected in microbial burden between copper formulations and stainless-steel coupons on microbiology laboratory benches where bacterial counts were low overall. All mass changes and corrosion rates of the formulations were acceptable by engineering standards. Copper surfaces vary in their antimicrobial efficacy after 1 year of hospital use. Frequency of cleaning and disinfection influence the impact of copper; the greatest reduction in microbial bioburden occurred in clinical areas compared to the microbiology laboratory where cleaning and disinfection were performed multiple times daily.

Super dosing copper (Cu) has long been used as an alternative to antibiotic growth-promoters in broiler chickens’ diet to improve gut health. This study was designed to compare nutritional and growth-promoting levels of Cu hydroxychloride (CH) with CuSO 4 on gut health bio-markers and liver mineral profile of broiler chickens. Ross 308 chicks ( n  = 864) were randomly assigned to eight treatments, as basal diet containing no supplemental Cu; the basal diet with 15 or 200 mg/kg Cu as CuSO 4 ; or 15, 50, 100, 150 or 200 mg/kg Cu from CH. The highest liver Cu content was observed in birds fed the diets with 200 mg/kg CuSO 4 ( P  < 0.01). Serum FITC-d concentration as the leaky gut marker, and liver malondialdehyde concentration were not affected. Copper level or source had no effect on cecal short chain fatty acid and the mRNA expression of five jejunal genes involved in gut integrity. Negative linear responses of Cu were observed on Lactobacillus ( P  = 0.032), Bacteroides ( P  = 0.033), and Enterobacteriaceae ( P  = 0.028) counts. The jejunal villus height increased in birds fed CH at 200 and 100 mg/kg ( P  < 0.05). Increasing Cu levels, linearly and quadratically ( P  < 0.001), increased Cu excretion.

The objective of the study was to evaluate the maximum tolerance limit of amino acid copper complex (Cu-Lys-Glu) for laying hens by measuring their laying performance, hematological and serum biochemical parameters, organ index, and histopathology. A total of 450 18-week-old Beijing White layers were randomly allocated to 5 groups (90 birds per group) with 6 replicates of 15 birds each. After a 2-week acclimation on a basal diet (analyzed copper content 8.63 mg/kg), the birds were fed diets supplemented with 0 (control), 15, 75, 150, and 300 mg Cu/kg as Cu-Lys-Glu for 10 weeks. Results showed that, compared with the control group, dietary supplementation with 15, 75, and 150 mg Cu/kg as Cu-Lys-Glu did not affect (P > 0.05) laying performance, whereas hens receiving with 300 mg Cu/kg significantly decreased (P < 0.001) the laying rate as compared with the control. No significant differences (P > 0.05) were observed among the hens receiving 0, 15, 75, and 150 mg Cu/kg as Cu-Lys-Glu in hematological and serum biochemical parameters, organ indexes, and histopathological changes. However, hens receiving 300 mg Cu/kg significantly increased (P < 0.05) the concentrations of mean corpuscular volume (MCV), albumin (ALB), total bilirubin (TBILI), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (UN), and creatinine (CRE), as well as caused severe microscopic histopathological changes in the liver and kidney. In conclusion, 150 mg Cu/kg as Cu-Lys-Glu is identified as no-side-effect supplementation level in laying hens after daily administration for 70 days.

Cow-calf operations may be affected by trace mineral deficiencies, particularly copper (Cu) and zinc (Zn) deficiency, which may decrease the calf daily weight gain and alter hematological parameters. We evaluated the effect of Cu and Zn supplementation on pre-weaning calves (n = 40; 92 ± 6 kg initial body weight) from the Salado River basin, Buenos Aires, Argentina. Calves were divided into four groups (n = 10 each) and subcutaneously administered 0.3 mg/kg Cu (Cu group), 1 mg/kg Zn (Zn group), Cu and Zn together (Cu + Zn group), and sterile saline solution (control group) every 40 days for 120 days. Plasma Cu and Zn concentrations, hematological parameters, and weight were recorded every 40 days. A completely randomized 2 × 2 factorial treatment design was used and data were analyzed with a mixed model for repeated measures over time. Cu and Zn were detected in plasma after the second sampling. Cu × Zn interaction was significant (p = 0.09), being Cu concentration higher in the Cu + Zn than in the Cu group. Differences in weight gain (Zn × time interaction; p < 0.01) were observed in the Zn but not in the Cu group (p > 0.1). On the other hand, none of the treatments altered any of the hematological parameters assessed (p > 0.1). Our results show the risk of lower weight gain due to Zn deficiency in pre-weaning calves raised in the Salado River basin.

Metabolic changes under stress are often studied in short-term experiments, revealing rapid responses in gene expression, enzyme activity, and the amount of antioxidants. In a long-term experiment, it is possible to identify adaptive changes in both primary and secondary metabolism. In this study, we characterized the physiological state of tobacco plants and assessed the amount and spectrum of phenolic compounds and the lignification of axial organs under excess copper stress in a long-term experiment (40 days). Plants were treated with 100 and 300 μM CuSO4, as well as a control (Knop solution). Copper accumulation, the size and anatomical structure of organs, stress markers, and the activity of antioxidant enzymes were studied. Lignin content was determined with the cysteine-assisted sulfuric method (CASA), and the metabolite profile and phenolic spectrum were determined with UHPLC-MS and thin-layer chromatography (TLC). Cu2+ mainly accumulated in the roots and, to a lesser extent, in the shoots. Copper sulfate (100 μM) slightly stimulated stem and leaf growth. A higher concentration (300 μM) caused oxidative stress; H2O2 content, superoxide dismutase (SOD), and guaiacol peroxidase (GPOX) activity increased in roots, and malondialdehyde (MDA) increased in all organs. The deposition of lignin increased in the roots and stems compared with the control. The content of free phenolics, which could be used as substrates for lignification, declined. The proportions of ferulic, cinnamic, and p-coumaric acids in the hydrolysate of bound phenolics were higher, and they tended toward additional lignification. The metabolic profile changed in both roots and stems at both concentrations, and changed in leaves only at a concentration of 300 μM. Thus, changes in the phenolic spectrum and the enhanced lignification of cell walls in the metaxylem of axial (root and stem) organs in tobacco can be considered important metabolic responses to stress caused by excess CuSO4.

Copper (Cu) is essential for many biological processes, but is toxic when present in excessive amounts. In this study, we provide evidence that Cu plays a crucial role in controlling tuberculosis. A Mycobacterium tuberculosis (Mtb) mutant lacking the outer membrane channel protein Rv1698 accumulated 100-fold more Cu and was more susceptible to Cu toxicity than WT Mtb. Similar phenotypes were observed for a M. smegmatis mutant lacking the homolog Ms3747, demonstrating that these mycobacterial copper transport proteins B (MctB) are essential for Cu resistance and maintenance of low intracellular Cu levels. Guinea pigs responded to infection with Mtb by increasing the Cu concentration in lung lesions. Loss of MctB resulted in a 1,000- and 100-fold reduced bacterial burden in lungs and lymph nodes, respectively, in guinea pigs infected with Mtb. In mice, the persistence defect of the Mtb mctB mutant was exacerbated by the addition of Cu to the diet. These experiments provide evidence that Cu is used by the mammalian host to control Mtb infection and that Cu resistance mechanisms are crucial for Mtb virulence. Importantly, Mtb is much more susceptible to Cu than other bacteria and is killed in vitro by Cu concentrations lower than those found in phagosomes of macrophages. Hence, this study reveals an Achilles heel of Mtb that might be a promising target for tuberculosis chemotherapy.

A 42-day experiment was conducted to evaluate the influence of dietary copper (Cu) concentrations on growth performance, nutrient digestibility, and serum parameters in broilers aged from 1 to 42 days. Five hundred forty 1-day-old broilers were randomly assigned into 1 of the following 6 dietary treatments: (1) control (basal diet without supplemental Cu), (2) 15 mg/kg supplemental Cu (Cu15), (3) 30 mg/kg supplemental Cu (Cu30), (4) 60 mg/kg supplemental Cu (Cu60), (5) 120 mg/kg supplemental Cu (Cu120), and (6) 240 mg/kg supplemental Cu (Cu240), Cu as copper methionine. A 4-day metabolism trial was conducted during the last week of the experiment feeding. The results showed that dietary Cu supplementation increased the average daily gain and the average daily feed intake ( P  < 0.01). The feed gain ratio, however, was not affected by dietary Cu ( P  > 0.10). Additionally, dietary Cu supplementation increased the digestibility of fat and energy ( P  < 0.05). The concentration of serum cholesterol, triglycerides, and high-density lipoprotein cholesterol decreased with dietary Cu supplementation ( P  < 0.05). The activities of serum Cu-Zn superoxide dismutase ( P  < 0.05), glutathione peroxidase ( P  < 0.05), and ceruloplasmin ( P  = 0.09), on the contrary, were increased by Cu addition. For immune indexes, dietary Cu supplementation increased serum IgA and IgM ( P  < 0.05). In addition, the activities of serum ALT increased with increasing dietary Cu supplementation ( P  < 0.05). In conclusion, our data suggest that Cu supplementation can increase fat digestibility and promote growth. Additionally, dietary Cu supplementation can reduce serum cholesterol and enhance antioxidant capacity in broilers.

Summary The growing demand for sustainable platforms for biomolecule manufacturing has fuelled the development of plant‐based production systems. Agroinfiltration, the current industry standard, offers several advantages but faces limitations for large‐scale production due to high operational costs and batch‐to‐batch variability. Alternatively, here, we describe the CuBe system, a novel bean yellow dwarf virus (BeYDV)‐derived conditional replicative expression platform stably transformed in Nicotiana benthamiana and activated by copper sulphate (CuSO4), an inexpensive and widely used agricultural input. The CuBe system utilizes a synthetic circuit of four genetic modules integrated into the plant genome: (i) a replicative vector harbouring the gene of interest (GOI) flanked by cis‐acting elements for geminiviral replication and novelly arranged to enable transgene transcription exclusively upon formation of the circular replicon, (ii) copper‐inducible Rep/RepA proteins essential for replicon formation, (iii) the yeast‐derived CUP2‐Gal4 copper‐responsive transcriptional activator for Rep/RepA expression, and (iv) a copper‐inducible Flp recombinase to minimize basal Rep/RepA expression. CuSO4 application triggers the activation of the system, leading to the formation of extrachromosomal replicons, expression of the GOI, and accumulation of the desired recombinant protein. We demonstrate the functionality of the CuBe system in N. benthamiana plants expressing high levels of eGFP and an anti‐SARS‐CoV‐2 antibody upon copper treatment. Notably, the system is functional in post‐harvest applications, a strategy with high potential impact for large‐scale biomanufacturing. This work presents the CuBe system as a promising alternative to agroinfiltration for cost‐effective and scalable production of recombinant proteins in plants.

Orthodontic archwires, especially nickel-titanium (NiTi) ones, are a major source of nickel release. Despite their importance, no in vivo studies have assessed the ion release from conventional or new generations of NiTi archwires (copper-included and epoxy-coated). This double-blind parallel randomized clinical trial was done on 84 saliva specimens sampled at two time points from 42 orthodontic patients. The patients were randomly divided into three groups of NiTi, copper NiTi (NiTiCu), and epoxy NiTi archwires ( n  = 14 each). The effects of 2-month treatment, wire types, gender, and age on pretreatment, posttreatment, and time-dependent differences were analyzed statistically ( α  = 0.05). Salivary nickel concentrations were 10.4571 ± 0.77168 and 11.0779 ± 0.81232 μg/L, respectively, in the baseline and second month. This increase was significant ( P  = 0.0000, paired t test). The extents of nickel increase in different groups were 0.8279 ± 0.14 (NiTi), 0.6493 ± 0.10 (NiTiCu), and 0.385 ± 0.11 (epoxy-coated NiTi) μg/L ( P  = 0.0000, one-way analyses of variance (ANOVA)). Differences between each two archwire types were significant ( P  = 0.000, Tukey). Age and gender did not play a role. It can be concluded that NiTi archwires might increase nickel salivary levels. Epoxy-coated NiTi followed by copper NiTi archwires might release less nickel compared to conventional NiTi ones.