Supplemental Doses Research Articles

Micronutrients at Supplemental Levels, Tight Junctions and Epithelial Barrier Function: A Narrative Review.

Disease modifiers, whether from cancer, sepsis, systemic inflammation, or microbial pathogens, all appear to induce epithelial barrier leak, with induced changes of the Tight Junctional (TJ) complex being pivotal to the process. This leak-and the ensuant breakdown of compartmentation-plays a central role in disease morbidity on many levels. Accumulation of lung water in the luminal compartment of airways was a major driver of morbidity and mortality in COVID-19 and is an excellent example of the phenomenon. Increasing awareness of the ability of micronutrients to improve basal barrier function and reduce barrier compromise in pathophysiology may prove to be a low-cost, safe, and easily administered prophylactic and/or therapeutic option amenable to large populations. The growing appreciation of the clinical utility of supplemental doses of Vitamin D in COVID-19 is but one example. This narrative review is intended to propose a general theory on how and why micronutrients-at levels above normal dietary intake-successfully remodel TJs and improve barrier function. It discusses the key difference between dietary/Recommended Daily Allowance (RDA) levels of micronutrients versus supplemental levels, and why the latter are needed in disease situations. It advances a hypothesis for why signal transduction regulation of barrier function may require these higher supplemental doses to achieve the TJ remodeling and other barrier element changes that are clinically beneficial.

Bacillus subtilis HW2 enhances growth performance and alleviates gut injury via attenuation of endoplasmic reticulum stress and regulation of gut microbiota in broilers under necrotic enteritis challenge

This study investigated the effects of Bacillus subtilis HW2 on the growth performance, immune response, endoplasmic reticulum (ER) stress, and intestinal health in broilers with necrotic enteritis. Three hundred 1-day-old male Cobb 500 broilers (33.88 ± 2.34 g) were randomly allocated to 5 groups including non-infected control (NC group), basal diet + necrotic enteritis challenge (NE group), basal diet + 1 × 106 CFU/g B. subtilis HW2 + necrotic enteritis challenge (L-Pro group), basal diet + 5 × 106 CFU/g B. subtilis HW2 + necrotic enteritis challenge (M-Pro group), and basal diet + 1 × 107 CFU/g B. subtilis HW2 + necrotic enteritis challenge (H-Pro group), with 6 replicates per group. All broilers except NC group were orally given with sporulated coccidian oocysts at day 14 and Clostridium perfringens from days 19 to 21. Results showed that L-Pro and M-Pro groups improved growth performance and intestinal morphology in necrotic enteritis-challenged broilers, and L-Pro, M-Pro, and H-Pro groups improved intestinal barrier function and immune response and decreased ER stress in necrotic enteritis-challenged broilers. Analysis of the gut microbiota revealed that L-Pro group increased the abundances of Alistipes, Coprobacter, Barnesiella, and Limosilactobacillus, decreased Erysipelatoclostridium abundance on day 42 in necrotic enteritis-challenged broilers. M-Pro group increased Turicibacter abundance on day 28 and the abundances of Alistipes, Barnesiella, and Limosilactobacillus on day 42 in necrotic enteritis-challenged broilers. H-Pro group decreased Romboutsia abundance on day 28 and unidentified_Clostridia abundance on day 42 in necrotic enteritis-challenged broilers. Analysis of short-chain fatty acids (SCFAs) revealed higher isobutyric acid and isovaleric acid levels in L-Pro and M-Pro groups than NE group. Correlation analysis revealed the correlations between the biochemical parameters and gut microbiota as well as SCFAs, especially Romboutsia, Barnesiella, Coprobacter, isobutyric acid, and isovaleric acid. Overall, our results indicated that B. subtilis HW2 supplementation could ameliorate necrotic enteritis infection-induced gut injury. The optimal dietary supplementation dosage of Bacillus subtilis HW2 was 5 × 106 CFU/g.

Restoration of Intestinal Microbiota After Inulin Supplementation Halted: The Secondary Effect of Supplemented Inulin.

Consumption of inulin could affect the intestinal microbiota composition. Hereby, it is aimed to investigate the intestinal microbial community restoration process when the inulin supplementation is terminated (i.e., the secondary effect). The current study investigates the response and restoration of intestinal microbiota to/after high (Inulin-H) and low (Inulin-L) dosage of inulin supplementation or sequential antibiotics and inulin (Anti-Inulin-L) supplementation, based on analysis of 16S rRNA gene sequences in C57BL/6 mice. The number of significantly changed genera in response to inulin is highest in Anti-Inulin-L (n=66) group, followed by Inulin-H (n=51) and Inulin-L (n=38) group. After inulin supplementation stops, microbiota of all studied groups tend to recover to their original states, with highest percentage of inulin-responding microbes stay significantly different at Anti-Inulin-L (93.94%) group, followed by Inulin-H (74.51%) and Inulin-L (44.12%) groups. Of note, the relative abundance of some non-inulin-responding taxa significantly increases during restoration. Sequential antibiotics and inulin supplementation induce greatest changes in the intestinal microbial composition, followed by high and low dosage of inulin. Additionally, the changes induce by supplemented inulin in the intestinal microbial community, provide a chance for some microbes to outcompete the other microbes during the spontaneous restoration.

Phytochemistry and antifatigue activities of Carica papaya leaf from geothermal, coastal and urban areas, Indonesia.

Fatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids, such as in the form of nutritional supplements. Papaya (Carica papaya) may be a potential candidate for ergogenic aids, considering its healthy secondary metabolite properties and number of metabolite compounds that could be affected by the location where the plant growing. The aim of this study was to identify the phytochemicals of papaya leaves from three different locations: geothermal, coastal, and urban areas in Aceh province, Indonesia. Concentrations of papaya leaf with the highest number of secondary metabolite compounds were tested in rats to measure blood lactate acid concentrations after strenuous exercise. The number of chemical compounds identified from the three locations was 24 compounds; 23 compounds and 17 compounds, respectively. The highest concentration of chemical compounds that have antifatigue activity contained in all papaya leaf samples were neophytadiene, linolenic acid, gamma tocopherol, hexadecanoic acid, vitamin E, carpaine, octadecatrienoic acid, nor lean-12-ene, squalene, and phytol. Furthermore, most of the compounds' highest concentrations were found in papaya leaves from the coastal area and, therefore, tested on the animal model. Treatment was provided in 12 male rats with different doses of papaya powder supplements for 15 days. The results showed that lactic acid levels of rats received a dose of 400 mg/kg of papaya leaf extract reduced the lactic acid concentration (p=0.014) compared with the control group. This study highlights that papaya leaves from the coastal area have the most potential activities as ergogenic herbal aid and were able to reduce lactic acid levels in rats after strenuous exercise.

Flavonoids as CYP3A4 Inhibitors In Vitro.

Flavonoids, a diverse group of polyphenolic compounds found abundantly in fruits, vegetables, and beverages like tea and wine, offer a plethora of health benefits. However, they have a potential interaction with drug metabolism, particularly through the inhibition of the cytochrome P450 3A4 enzyme, the most versatile and abundant enzyme in the liver. CYP3A4 is responsible for metabolizing approximately 50% of clinically prescribed drugs across diverse therapeutic classes, so these interactions have raised concerns about potential adverse effects. This review delves into the scientific evidence surrounding flavonoid-mediated CYP3A4 inhibition, exploring the inhibitory potential of investigated flavonoids and future implications. Kusehnol I, chrysin, leachianone A, and sophoraflavone G showed the largest inhibitory potentials and lowest IC50 values. While the clinical significance of flavonoid-mediated CYP3A4 inhibition in dietary contexts is generally considered low due to moderate intake and complex interactions, it poses a potential concern for individuals consuming high doses of flavonoid supplements or concurrently taking medications metabolized by CYP3A4. This can lead to increased drug exposure, potentially triggering adverse reactions or reduced efficacy.

Limosilactobacillus reuteri peptidoglycan alleviates aflatoxin B1-induced toxicity through adsorbing toxins and improving growth, antioxidant status, immunity and liver pathological changes in chicks

ABSTRACT 1. The objective of this study was to investigate the protective effects of a peptidoglycan produced by Limosilactobacillus reuteri against aflatoxin B1 (AFB1) induced toxicity in vitro and in vivo in broiler chicks. 2. Toxin adsorption experiments were carried out firstly in vitro. These experiments indicated that the absorption efficiency of the peptidoglycan for AFB1 was 64.3–75.9%. 3. In the in vivo experiments, Hy-Line Brown chicks were fed a diet containing AFB1 at 71.43 µg/kg with and without peptidoglycan supplementation at concentrations of 100, 200, or 300 g/kg feed from 0–42 d of age. 4. The peptidoglycan supplementation in AFB1-contaminated diets resulted in significant improvements in terms of average daily gain, feed intake, feed conversion ratio, white blood cell count, haemoglobin content, glutathione peroxidase activity, immunoglobulin (Ig) A, IgG, IgM and Newcastle disease virus antibody titres (p < 0.05) and diminished liver steatosis. 5. In conclusion, peptidoglycan supplementation alleviated AFB1-induced toxicity through adsorbing toxins and improving growth performance, antioxidant ability, immunity and liver pathological changes in chicks. The optimal supplemental dose was 200 mg/kg in feed.

The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D3 supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D3 supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D3 supplementation on immune gene expression.

The Effect of Short-Term NAD3® Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 Years.

Objective This study aimed to assess the impact of acute and short-term supplementation with NAD3®, a theacrine-containing supplement, on circulating adult stem cell numbers in a healthy male and female population aged 40-70 years. Methods This was a double-blind, placebo-controlled crossover study with 12 participants randomized to receive either NAD3® or a placebo for seven days. Blood samples were collected after an overnight fast, before and after the seven-day supplementation period, and one and two hours after the final supplement dose. Using flow cytometry, circulating stem cells, including lymphocytoid CD34+stem cells (CD45dimCD34+), stem cells associated with vascular maintenance and repair (CD45dimCD34+CD309+), CD34+stem cells linked to a progenitor phenotype (CD45dimCD34+CD309neg), circulating endothelial stem cells (CD45negCD31+CD309+), and mesenchymal stem cells (CD45negCD90+) were quantified. Results Acute NAD3®supplementation did not result in the mobilization of stem cells from the bone marrow. However, seven days of daily NAD3®supplementation resulted in selective changes in circulating stem cell numbers. A significant time*treatment interaction was observed for CD45dimCD34+cells (p=0.04) and CD45dimCD34+CD309negcells (p=0.04), indicating a decrease in cell numbers with supplementation. There was also a trend toward an increase in circulating endothelial cells (p=0.08) with seven days of NAD3®supplementation. Conclusion Short-term NAD3® supplementation demonstrated an effect on the quantity of bone marrow-derived stem cells in circulation. The study suggests that this theacrine-containing supplement may play a role in modulating adult stem cell populations, emphasizing the potential impact of NAD3® on regenerative processes. Further research with extended supplementation periods and larger sample sizes is warranted to elucidate the functional consequences of these changes and explore the therapeutic implications for age-related declines in stem cell function.

Appropriate dose of NaCl supplementation improves protein structures, microbial communities and extensibility of dough, and quality of traditional fermented dried noodles

AbstractBackground and ObjectivesIn the production process of Zhongjiang traditional fermented dried noodles (TFDNs), about 10% of NaCl is added; however, the underlying mechanisms of its effects remain unclear. Thus, this study aimed to investigate the impact of varying NaCl concentrations (6%–14%) on protein conformation, tensile and rheological properties, microbial communities in the dough, and quality of the dried noodles.FindingsThe results indicated that 6%–10% NaCl supplementation increased the ordered structures, disulfide bond contents, rheological parameters, the abundance of Pantoea and cumulative abundance of Mitochondria and Chloroplast in the dough, and reduced bacterial diversity and disordered structures; 8%–10% NaCl enhanced tensile properties of dough, cooking quality, and sensory attributes of noodles; cooked noodles with 10% NaCl had the best hardness, adhesiveness, springiness, and chewiness. However, excessive NaCl (12%–14%) did not confer these benefits. Furthermore, dough containing 6% NaCl exhibited excessive stickiness and reduced tensibility, rendering it unsuitable for making dried noodles.ConclusionsThe addition of 8%–10% NaCl improved protein structural properties and bacterial community in the dough and ultimately elevated the extensibility of the dough and the quality of TFDN.Significance and NoveltyThese findings reveal the potential mechanisms of NaCl in the processing of TFDN and lay a foundation for producing healthier TFDN with lower sodium in the future.

Impact of radiation dose distribution on nutritional supplementation needs in head and neck cancer radiotherapy: a voxel-based machine learning approach.

To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy. We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient's anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated. DIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictor muscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation. Machine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx.

Exploring the link between vitamin D deficiency and obstructive sleep apnea: A comprehensive review.

Despite the high prevalence and significant health burden of obstructive sleep apnea (OSA), its underlying pathophysiology remains incompletely understood. This comprehensive review explores the emerging connection between vitamin D deficiency and OSA, discusses potential mechanisms underlying this association, and explores the therapeutic implications of these findings. Recent research has consistently highlighted the high incidence of vitamin D deficiency among patients with OSA, which often occurs independently of geographical location. This suggests that factors beyond lack of sunlight exposure may be involved. This review also discusses how reduced vitamin D may be associated with more severe manifestations of OSA. In addition, it explores the potentiality of using vitamin D supplements as a therapeutic strategy for OSA, noting that some studies have found improvements in sleep quality and a reduction in OSA severity. Potential mechanisms are proposed, including the role of vitamin D deficiency in promoting inflammation, oxidative stress, hypoxia, impairing immune function, muscle function, and gene polymorphism of vitamin D receptors, all of which could contribute to the pathogenesis of obstructive sleep apnea. The paper underscores the need for future research to validate these observations, to determine optimal vitamin D supplementation dosage and duration, to explore potential side effects and risks, and to investigate potential interactions with other treatments.

Individuals Diagnosed With Type 2 Diabetes Mellitus and the Status of Vitamin B12 Deficiency: A Review.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a multifactorial etiology and a significant global burden. In recent years, emerging evidence has suggested a potential link between T2DM and vitamin B12 deficiency, raising concerns about its impact on disease progression, management, and associated complications. This comprehensive review critically examines the current understanding of the prevalence, risk factors, clinical implications, and management strategies related to vitamin B12 deficiency in individuals diagnosed with T2DM. The review begins by providing an overview of the epidemiology of T2DM and its associated complications, underscoring the need for comprehensive management approaches. Subsequently, it delves into the physiology of vitamin B12, including its sources, absorption mechanisms, and biological functions, laying the groundwork for understanding the potential implications of deficiency in T2DM. A thorough analysis of the literature is conducted to elucidate the prevalence and risk factors of vitamin B12 deficiency in individuals with T2DM, considering factors such as age, duration of diabetes, medication use (e.g., metformin), dietary patterns, and comorbidities. Special attention is given to the role of metformin, the first-line therapy for T2DM, in precipitating or exacerbating vitamin B12 deficiency through mechanisms involving alterations in the gut microbiota and intestinal absorption. The review further explores the clinical manifestations and diagnostic challenges associated with vitamin B12 deficiency in the context of T2DM, emphasizing the importance of recognizing subtle symptoms and implementing appropriate screening protocols. It discusses the potential implications of vitamin B12 deficiency on glycemic control, diabetic neuropathy, cognitive function, cardiovascular health, and overall quality of life in individuals with T2DM. In addressing the management of vitamin B12 deficiency in T2DM, the review examines various therapeutic strategies, including oral and parenteral supplementation, dietary modifications, and lifestyle interventions. It critically evaluates the evidence supporting routine screening for vitamin B12 deficiency in individuals with T2DM and discusses controversies surrounding optimal supplementation protocols, dosing regimens, and monitoring strategies. Furthermore, the review highlights gaps in current knowledge and identifies areas for future research, such as the long-term effects of vitamin B12 supplementation on clinical outcomes in T2DM, the impact of genetic factors on vitamin B12 metabolism, and the potential role of personalized interventions. Overall, this review consolidates existing evidence and provides insights into the complex relationship between T2DM and vitamin B12 deficiency, aiming to inform clinical practice, enhance patient care, and guide future research endeavors in this important area of metabolic medicine.

Magnitude and determinants of adherence to iron-folic acid supplementation among Somaliland pregnant women in Ahmed-dhagah district: A facility based cross-sectional study

BackgroundIron deficiency is a major cause of anemia globally, especially in low-income countries, and pregnant women are at higher risk. Despite guidelines recommending IFA supplementation, adherence remains low. Therefore, the aim of this study is to assess the adherence to iron-folic acid (IFA) supplementation among pregnant women receiving antenatal care services in the Ahmed-Dhagah district, Hargeisa, Somaliland. MethodsA cross-sectional study was conducted at an institutional level from May to July 2022. A systematic sampling method was used to select 320 pregnant women. Data collection was performed using the Kobo Collect Android app, and the data were analyzed using SPSS. Descriptive statistics, bivariate analysis, and multivariable logistic regression analysis were employed to identify independent variables associated with adherence to IFA supplementation. Statistical significance was determined using a p-value <0.05. ResultsOnly 74 (24%) women adhered to ≥ 65% of the recommended IFA supplement doses, equivalent to more than four days a week. In the multivariate logistic regression model, the husband's educational status (AOR = 8.468, 95% CI: 3.436, 20.87), number of antenatal care visits (AOR = 3.385, 95% CI: 1.55, 7.39), and maternal knowledge about anemia (AOR = 3.534, 95% CI: 1.739, 7.194) were identified as factors significantly associated with good adherence to IFA supplementation. ConclusionThe pregnant women's adherence to IFA supplementation was very low compared to WHO guidelines. Factors like the husband's education, antenatal care visits, and maternal knowledge of anemia affected adherence. Common reasons for non-compliance included forgetfulness, drug side effects, and fear of side effects.

Impacts of micro- to nano-sized carbon supplements on mixed and archaea-free halophilic cultures when used for bioenergy recovery from saline wastewater

Due to the growing interest in enhancing dark fermentation and anaerobic digestion via carbon-based additives to exploit different lucrative synergies, process-based optimizations and mechanistic analyses are crucial. Herein, we studied the impacts of carbon supplements on halophilic microbial cultures as a process intensification way towards bioenergy recovery from saline wastewater. Three additives, i.e., powdered activated carbon, multiwall carbon nanotubes and graphene, were examined. Two sets of parallel batch experiments were conducted using archaea-free (for dark fermentation) and mixed (for anaerobic digestion) halophilic cultures at different supplement doses. Adding 30 mg/L of graphene and 100 mg/L of powdered activated carbon exhibited the maximum improvements in dark fermentation (H2-production) and anaerobic digestion (biogas production), i.e., ∼28% and ∼27% over the control, respectively. This underscored the dose-dependent impact of different-sized carbon amendments. Both the electron transport system activity and extracellular polymeric substances were improved with all amendments, indicating a stimulated electron transfer flux. However, distinct bacterial compositions were identified when using mixed and archaea-free cultures along with indicators for direct interspecies electron transfer establishment in the presence of archaea. Beyond this, such findings also supported the expanded role of conductive additives on H2-producing bacteria, including Clostridium. According to a techno-economic analysis, powdered activated carbon emerged as the best for optimizing bioenergy recovery (in terms of H2 or biogas) from saline wastewater, providing a solid basis for relevant applications.

The effects of omega-3 fatty acids supplementation on hemoglobin, hematocrit, and platelet levels of patients with ESRD condition undergoing dialysis

BackgroundConcomitant inflammation may boost the cardiovascular complications in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). Omega-3 fatty acids may have certain health benefits in HD patients. The aim of this study was to investigate the effects of omega-3 fatty acids supplementation on hematocrit (HCT), hemoglobin (HB) level and platelet (PLT) counts of HD patients. MethodsA randomized controlled trial was conducted on HD patients at a private dialysis center in Rasht, Iran. Three omega-3 fatty acid supplement capsules (3 g/d) were administered daily for two months to patients in the intervention group (n = 55). The control group (n = 60) were given three placebo capsules containing medium chain triglyceride (MCT) oil, similar to the supplemental dose of the intervention group at the same period. Three parameters of HCT, HB and PLT were measured at baseline and after the intervention. ResultsThe PLT count decreased in the intervention group compared to the control group (173.38 ± 74.76 vs. 227.68 ± 86.58 103/mm3, F = 4.83, P = 0.03). No significant change was found on the levels of HCT and HB parameters between the two groups after the intervention. ConclusionOmega-3 supplementation in HD patients may decrease the risk of forming blood clots in the blood vessels. Further studies are warranted.

Raman spectroscopy study of 7,8-dihydrofolate inhibition on the Wuhan strain SARS-CoV-2 binding to human ACE2 receptor

Emerging evidence suggests that elevated levels of folic acid in the bloodstream may confer protection against Wuhan-SARS-CoV-2 infection and mitigate its associated symptoms. Notably, two comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals with heightened folic acid levels exhibited only mild symptoms and necessitated no ventilatory support. In parallel, research has underscored the potential connection between decreased folic acid levels and the severity of Covid-19 among hospitalized patients. Yet, the underlying mechanisms governing this intriguing inhibition remain elusive. In a quest to elucidate these mechanisms, we conducted a molecular dynamics simulation approach followed by a Raman spectroscopy study to delve into the intricate interplay between the folic acid metabolite, 7,8-dihydrofolate (DHF), and the angiotensin-converting enzyme ACE2 receptor, coupled with its interaction with the receptor-binding domain (RBD) of the Wuhan strain of SARS-CoV-2. Through a meticulous exploration, we scrutinized the transformation of the ACE2 + RBD complex, allowing these reactants to form bonds. This was juxtaposed with a similar investigation where ACE2 was initially permitted to react with DHF, followed by the exposure of the ACE2 + DHF complex to RBD. We find that DHF, when bonded to ACE2, functions as a physical barrier, effectively inhibiting the binding of the Wuhan strain RBD. This physicochemical process offers a cogent explanation for the observed inhibition of host cell infection in subjects receiving supplementary folic acid doses, as epidemiologically substantiated in multiple studies. This study not only sheds light on a potential avenue for mitigating SARS-CoV-2 infection but also underscores the crucial role of folic acid metabolites in host-virus interactions. This research paves the way for novel therapeutic strategies in the battle against COVID-19 and reinforces the significance of investigating the molecular mechanisms underlying the protective effects of folic acid in the context of viral infections.

Effects of resveratrol on the anthropometric indices and inflammatory markers: an umbrella meta-analysis.

The evidence for resveratrol's anti-obesity and anti-inflammatory qualities is accumulating, though meta-analyses have reported mixed results. The current umbrella meta-analysis aimed to assess the present evidence and provide an accurate estimate of the overall effects of resveratrol on the anthropometric indices and inflammatory markers. The Web of Science, PubMed, Scopus, and Google Scholar databases were searched till March 2023. The meta-analysis was performed utilizing a random-effects model. Moreover, the overall strength and quality of the evidence were assessed using the GRADE tool. The results from 19 meta-analyses investigating 81 unique randomized controlled trials with 4088 participants revealed that resveratrol supplementation reduced the body mass index (ES = - 0.119, 95% CI (- 0.192, - 0.047), p = 0.001), waist circumference (ES = - 0.405, 95% CI [- 0.664, - 0.147], p = 0.002), serum levels of C-reactive protein (ES = - 0.390, 95% CI [- 0.474, - 0.306], p < 0.001), and tumor necrosis factor-α (ES = - 0.455, 95% CI [- 0.592, - 0.318], p < 0.001) in comparison to the control group. The effects of resveratrol on body weight and Interleukin-6 levels of participants were not significant. However, resveratrol administration significantly decreased body weight in trials with intervention duration ≥ 12 weeks [ES = - 0.160, 95% CI (- 0.268, - 0.052)] and supplement dosage ≥ 500 mg/day [ES = - 0.130, 95% CI (- 0.238, - 0.022)]. The findings suggest the beneficial effects of resveratrol supplementation on reducing general and central obesity, as well as decreasing some inflammatory markers. Nevertheless, further high-quality research is required to prove these achievements and also evaluate resveratrol's effects on other inflammatory markers.

The magnitude of the plasma hepcidin response to oral iron supplements depends on the iron dosage.

Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production. Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose. Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9;p< 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2= 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2= 0.529, p = 0.002). We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).

Mixing approach for 3D printable concrete: method of optimisation of superplasticiser dosage

This study is a systematic investigation of superplasticiser (SP) addition methods and optimum SP dosage with various water-to-binder ratios (w/b) for mixing three-dimensional printable concrete. In this study, five distinct strategies were adopted to arrive at the optimum method of addition. In the first strategy, a random mixing approach was applied to identify, through visual observation, methods for adding SP with varying time patterns. Secondly, a constant time pattern was adopted from the random approach for mixing and the optimal SP dosage was determined. In the third strategy, different methods of adding the optimum SP dosage were examined. In the fourth strategy, the batching effect of the material with the optimum SP dosage was assessed. Finally, the printable regions with different values of w/b and SP dosages were correlated. It was observed that the optimum SP dosage, in the range of 0.10–0.21% of binder, with w/b = 0.21–0.25 achieved adequate printability parameters by full addition of SP following a constant wet mixing time as the optimal application. However, after applying the optimum SP dosage, a supplemental SP dosage is required at appropriate intervals to retain the workability for higher batches.

The effect of taking doses of magnesium supplements on the development of the enzyme (CPK) and the achievement of 100 m freestyle swimming among young men

The aim of the study is to identify the effect of magnesium supplementation in the development of CPK for young men's backgammon. The study was conducted on a sample of the national youth team swimmers for short distances (100) m free and there were (10) swimmers. The pilot experiment was conducted on two swimmers from the main research sample and after providing all the necessary requirements and requirements for the implementation of the research program, the researcher, in collaboration with the national youth coach, conducted a pre-test involving the withdrawal of a blood sample from the hand by 5 cc. 100 m After the completion of the test and recording the results in a special form was given the amount of prescribed doses of magnesium to swimmers in the prescribed period with the application of the vocabulary of the training program prepared by the trainer and approved by the Central Iraqi Swimming and The researcher concluded that the magnesium supplementation doses used by the swimmers were useful for raising the level of the CPK enzyme in the blood and thus raising the achievement level in the research sample in swimming pool 100 m. The researcher recommended the selection of appropriate dietary supplements that fit The level of players, the training age of the swimmers, their levels and the training objective for which they were set up