Search Results (223)

Background/Objectives: Pomegranate (Punica granatum) peel, often discarded as waste, contains abundant bioactive compounds such as polyphenols, vitamins, flavonoids, tannins, anthocyanins, and many more. This contributes to remarkable bioactivities, including anticancer, anti-inflammatory, antioxidant, antibacterial, and antifungal properties. Pancreatic cancer is a deadly cancer with a 9% survival rate. Its aggressiveness, invasiveness, quick metastasis, and poor prognosis significantly decrease the survival rate. Thus, we aim to explore pomegranate peel as a possible alternative medication for treating pancreatic cancer through virtual methods. Methods: Firstly, bioactive compounds were collected from multiple databases and screened for oral bioavailability (OB) ≥ 0.3 and drug likeness (DL) ≥ 0.18 scores. Simultaneously, network pharmacology was employed to extract the most probable targets for pancreatic cancer. Further computational analyses were performed, including molecular docking, molecular dynamics simulation, and in silico pharmacokinetics evaluation. Results: Consequently, the top 10 key targets from network analysis were AKT1, IL6, TNF, SRC, STAT3, EGFR, BCL2, HSP90AA1, HIF1A, and PTGS2. However, only AKT1, EGFR, BCL2, HSP90AA1, and PTGS2 exhibited strong binding affinities with pomegranate compounds, which are significantly declared in affected cells to enhance cancer progression. Outcomes from molecular dynamics simulations, particularly RMSD, RMSF, hydrogen bonding, and radius of gyration (Rg), confirmed stable interactions between 1-O-Galloyl-beta-D-glucose, epicatechin, phloridzin, and epicatechin gallate with respective target proteins. Conclusions: This suggests that pomegranate peels hold anticancer bioactive compounds for treating pancreatic cancer. Surprisingly, most compounds adhere to Lipinski’s and Pfizer’s rules and display no toxicity. However, as this study relies entirely on computational methods, experimental validation is necessary to confirm these findings and assess real-world efficacy and potential side effects. Full article

Vitamin D is a key micronutrient in the function of the skeletomuscular system. Athletes are at increased risk of developing vitamin D deficiency during the execution of very demanding disciplines such as CrossFit^®. Single-nucleotide polymorphisms (SNPs) may influence circulating 25-hydroxy-vitamin D (25(OH)D) levels. An observational, longitudinal pilot study was conducted with 50 trained males according to specific inclusion criteria. Blood samples were obtained to determine 25(OH)D, vitamin D-binding protein (VDBP), vitamin D-receptor (VDR)circulating levels, and the presence of SNPs after DNA isolation and genotyping: rs10741657 to CYP2R1, rs2282679 to GC and rs2228570 to VDR genes. Significant differences (p < 0.05) in 25(OH)D concentration were determined between the biallelic combinations of rs228679 (GC) and rs228570 (VDR). The VDBP and VDR proteins did not show different levels in the case of the rs10741657 (CYP2R1) alleles. Statistically significant weak positive correlations (p < 0.05) were observed between 25(OH)D and AA-alleles of the CYP2R1 and VDR genes, and TT-alleles of the GC gene. Additionally, AA (rs10741657 and rs2228570) and TT (rs2282679) have a probability between 2 and 4 of having major effects on the concentration of 25(OH)D. Conversely, GG alleles present a probability of suboptimal values of 25(OH)D of 69%, 34%, and 24% for VDR, GC, and CYP2R1, respectively, showing a strong moderate positive correlation (r = 0.41) between the degrees of sports performance and 25(OH)D plasma levels. CYP2R1 (rs10741657), GC (rs2282679), and VDR (rs2228570) affect the concentration of serum 25(OH)D, as an indicator of vitamin D status and play a critical role in the sports performance of CrossFit^® practitioners. Full article

Multiple Sclerosis (MS) is a chronic disease with autoimmune and neurodegenerative features that affect the nervous system. Genetic predisposition and environmental factors, such as vitamin D deficiency and dysbiosis activating a pro-inflammatory response, have a role in the etiology of the disease. In this context, the interactions of vitamin D with the gut microbiota and immune system have attracted attention in recent years. Vitamin D (1,25-dihydroxycholecalciferol) modulates the immune response by binding to the Vitamin D receptor (VDR). This pathway supports the functions of regulatory T cells by suppressing the activity of T helper cells 1 and 17 (Th1 and Th17). In MS patients, dysbiosis is characterized by a decrease in microbial diversity, and an increase in pro-inflammatory species is observed when compared to healthy individuals. Vitamin D has protective effects on eubiosis via VDR in intestinal epithelial cells, also reducing intestinal permeability by regulating tight junction proteins. In this way, vitamin D may contribute to the prevention of systemic inflammation. Although the relationship between vitamin D and the immune system is well documented, studies that address the triad of vitamin D level, gut microbiota, and immune response in MS are still limited. Full article

Background/Objectives: Anemia, particularly iron-deficiency anemia (IDA), and stunting remain notable early childhood public health challenges in Indonesia; however, studies are still scarce. This study aimed to determine the co-occurrence of anemia and stunting (CAS), their prevalence, and the associated factors, as well as to describe the erythrocyte parameters. Methods: Approximately 2200 children aged 6–24 months were identified by midwives to have problematic nutritional status at Bandung Regency, West Java, Indonesia. These children were included in the population frame for a cohort study of vitamin D deficiency, vitamin D binding protein, and its impact on neurodevelopmental functions. A cross-sectional study was nested in the cohort study. The subjects were selected by stratified random sampling of 270 villages to meet the required number of samples. Medical doctors reassessed the anthropometric measurements and performed guided interviews to collect associated factors for IDA and CAS. Erythrocyte profiles of the children were examined from venous blood. Results: One hundred and ninety-four subjects were included in the analysis, among which 54.1% were stunted. Anemia was present in 40.7% of the subjects, largely due to IDA (87.3%). A wasting child and the factor of low paternal education (up to elementary school) were associated with IDA (aOR of 7.12 and aOR of 3.32, p < 0.05, respectively). Co-occurrence of anemia and stunting was found in 41/194 (21.1%) subjects, but it did not show significant association. Conclusions: Anemia and stunting were prevalent among children aged 6–24 months, but no associations were found between anemia and stunting in this study. Iron deficiency was the main cause of anemia, and it was associated with wasting and low paternal education. Full article

Preterm birth (PTB; <37 weeks’ gestation) is a persistent problem in the United States that affects non-Hispanic Black women at much higher rates than White women. Several biomarkers have been associated with PTB, including vitamin D deficiency (VDD) and low levels of vitamin D-binding protein (VDBP). However, no biomarker has been found to predict PTB. To identify a predictive biomarker of PTB, gene expression differences were determined in Black women with PTB and full-term births and between women with high and low levels of plasma vitamin D and high and low VDBP levels. In this pilot study of 19 pregnant women from the Biosocial Impact on Black Births (BIBB) study, we found that 47 genes were upregulated and 16 genes were downregulated in women with PTB as compared with women who had a full-term birth, 361 genes were downregulated and 61 genes were upregulated in women with VDD as compared with those that had vitamin D sufficiency, and 44 genes were upregulated and 295 were downregulated in women with low VDBP. Several genes expressed by neutrophils were downregulated in the PTB, VDD, and low VDBP groups. These findings support the idea that vitamin D and VDBP status may be important clinical markers influencing the gene expression of genes associated with PTB. Full article

Intact parathyroid hormone (PTHi) plays a central role in the regulation of mineral and bone metabolism. Due to post-translational modifications of the hormone, the interpretation of elevated PTHi values is challenging and may benefit from an expanded analytical panel. Within this project, additional parameters of calcium–phosphate metabolism, such as non-oxidised parathyroid hormone (noxPTH), calcidiol, vitamin D binding protein (VDBP), and fibroblast growth factor 23 (FGF23) were evaluated in a control population of 177 individuals as well as 182 patients with renal, gastroenterological, and liver diseases. While PTHi and noxPTH levels were up to 10-fold higher in dialysis patients, the proportion of noxPTH on PTHi was significantly higher for all patient groups showing signs of inflammation. However, no strong confounders for PTHi could be identified. The correlation between CRP and the proportion of oxidised PTHi in total PTHi suggests an influence of inflammatory oxidative stress on the proportion of active noxPTH. Apart from the established role of vitamin D, the addition of noxPTH and its proportion of total PTHi in the assessment of unclear PTHi elevations seems reasonable, whereas there is no evidence for the standardised analysis of further parameters such as FGF23 and VDBP. Full article

Background: In humans, vitamin D₃ synthesis follows a day–night rhythm due to its UV-B-dependent production. Results: As part of the VitDHiD intervention study, we identified 87 in vivo vitamin D target genes with circadian expression patterns in immune cells, forming a regulatory network centered on transcription factors and membrane receptors. These genes exhibit a narrow basal expression range, with 80% downregulated upon vitamin D₃ supplementation. Clustering analysis revealed six distinct gene groups, with the two most prominent clusters driven by the transcription factor CSRNP1 (cysteine- and serine-rich nuclear protein 1) and GAS7 (growth arrest-specific 7), a known differentiation inducer. Among the 25 VitDHiD study participants, we identified two subgroups distinguished by significant differences in the responsiveness of 14 in vivo vitamin D target genes. These genes encode transcription factors like CSRNP1, as well as metabolic enzymes and transporters, including NAMPT (nicotinamide phosphoribosyltransferase), PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), and SLC2A3 (solute carrier family 2 member 3). Notably, all 14 genes possess a vitamin D receptor-binding enhancer within a reasonable distance of their transcription start site. Conclusions: These findings highlight a novel link between vitamin D signaling and circadian gene regulation, with potential implications for personalized supplementation strategies. Full article

Acute kidney injury (AKI) is a common critical clinical disease with high morbidity and mortality rates. Ischemia-reperfusion (IR) is the main cause of AKI, and there is no effective treatment or prevention. Therefore, it is critical to screen for effective therapeutic agents and to find therapeutic targets. DKS26 is a derivative of oleanolic acid (OA) optimized for bioavailability while retaining the anti-inflammatory, antioxidant, and anti-apoptotic properties of OA. This study aimed to investigate the therapeutic effects of DKS26 on AKI and its underlying molecular mechanisms. We established an AKI model in vivo and in vitro and observed that DKS26 had an ameliorative effect on IR or H/R-induced renal tubular epithelial cell injury and reduced oxidative stress, inflammation, and apoptosis. Meanwhile, Swiss TargetPrediction and AutoDock Vina analysis revealed that DKS26 may interact with vitamin D receptors (VDR) through hydrogen bonding, suggesting that DKS26 may exert effects through VDR. In this study, we found that DKS26 treatment enhanced the stability of the VDR protein, promoted the binding of VDR to p-NF-κB P65^Ser311, reduced the entry of p-NF-κB P65^Ser311 into the nucleus, and inhibited the transcription of downstream inflammatory genes as well as their own expression, thus exerting its protective effect. In summary, these findings suggest that DKS26 may be a promising preventive strategy and provide a theoretical and experimental basis for AKI treatment. Full article

Vitamin D is crucial for immune regulation, and its deficiency is linked to multiple sclerosis (MS). The GC gene encodes Vitamin D Binding Protein (VDBP), which regulates vitamin D transport and bioavailability. This study examines the association of GC polymorphisms (rs7041, rs4588) with MS susceptibility and their impact on 25-hydroxyvitamin D [25(OH)D] levels in a Latvian cohort. This case–control study included 296 MS patients and 253 healthy controls. Genotyping of rs7041 and rs4588 was conducted using restriction fragment length polymorphism analysis and validated by Sanger sequencing. Plasma 25(OH)D levels were measured in 131 MS patients using an enzyme-linked immunosorbent assay. Statistical analysis included Hardy–Weinberg equilibrium testing, Fisher’s exact test, allelic and genotypic frequency comparisons to assess MS risk, and the Kruskal–Wallis test for 25(OH)D level differences among genotypes. Our findings indicate that the rare rs7041-T and rs4588-A alleles, along with their corresponding haplotypes, exhibit a protective effect against MS (p < 0.001; OR = 0.65 for rs4588-A; p < 0.01; OR = 0.70 for rs7041-T). Conversely, the common rs7041-G and rs4588-C alleles were associated with an increased MS risk (p < 0.05). Individuals with the Gc1F/1F isotype had the highest average 25(OH)D levels (29.31 ng/mL), while Gc1S/2 carriers had the lowest (21.53 ng/mL). Our results indicate that GC polymorphisms may influence the susceptibility of Latvians to MS and vitamin D status. Full article

Objectives: The aim was to simultaneously investigate inflammatory biomarkers, neopterin, the kynurenine/tryptophan (Kyn/Trp) pathway, vitamin D (VitD), vitamin D binding protein (VDBP), and erythrocyte folate, in cerebral palsy (CP). Methods: A case–control study was conducted at Mersin University Hospital. Three- to ten-year-old patients with spastic CP (n = 50) and age- and gender-matched healthy controls (n = 55) were included. Serum levels of neopterin, Trp, Kyn and 25OHD, plasma VDBP, and erythrocyte folate concentrations were measured. Indoleamine-2,3-dioxygenase 1 (IDO-1) enzyme activity was evaluated according to the Kyn/Trp ratio. Comparison and correlation analyses were performed. Results: The levels of neopterin, Trp, and Kyn were lower in children with CP than in healthy controls (p = 0.037, p < 0.001, and p = 0.003, respectively). IDO1 was not significantly different between the CP and control groups (p = 0.214). The levels of VitD and VDBP were higher in children with CP (p < 0.001 and p = 0.001, respectively). The level of erythrocyte folate was also higher in children with CP (p < 0.001). No significant correlation was found between age and inflammatory biomarkers in the CP group. Neopterin was correlated with the level of Gross Motor Function Classification System (GMFCS) level (r = 0.292, p = 0.044), while there was no significant correlation between the other biomarkers and the level of GMFCS in the CP group. Conclusions: Inflammatory biomarkers of neopterin and Kyn are lower, inflammatory biomarkers of VDBP and erythrocyte folate are higher, and anti-inflammatory VitD is higher in children with spastic CP compared to healthy children. More knowledge is needed to demonstrate inflammatory and anti-inflammatory status in children with CP. Full article

Despite the end of the COVID-19 pandemic, there still remain risks of new aggressive strains of coronavirus. As the human population increases progressively, it is mandatory to ensure both preventive measures and an immediate response to emerging infectious threats. Another essential component for rapidly restraining a new possible pandemic is the development of new anticoronaviral therapeutics. In the present study, the anticoronaviral capabilities of Gc protein-derived macrophage-activating factor (GcMAF) are characterized. It is demonstrated that the administration of GcMAF to Syrian hamsters infected with SARS-CoV-2 within the first phase of infection (six days postinfection) is accompanied by (i) a statistically significant reduction in the viral load of the lung tissue and (ii) the switching of the inflammatory status of the lung tissue to a neutral one in terms of mRNA expression levels of the groups of pro/anti-inflammatory cytokines and chemokines. The potential mechanism for this antiviral action and the containment of the inflammatory response by the drug associated with the engagement of terminal N-acetylgalactosamine GcMAF and C-type lectin domain containing 10A expressed at the surface of lung-infiltrating macrophages and pneumocytes, which simultaneously express angiotensin-converting enzyme 2, is discussed. Full article

Background: This study aimed to investigate genetic variants associated with the estimated glomerular filtration rate (eGFR) and their interactions with lifestyle factors and bioactive compounds in large hospital-based cohorts, assessing their impact on renal dysfunction risk. Methods: Participants were categorized into two groups based on eGFR: High-GFR (control; n = 51,084) and Low-GFR (renal dysfunction; n = 7617), using an eGFR threshold of 60 mL/min/1.73 m². Genetic variants were identified through a genome-wide association analysis, and their interactions with lifestyle factors were assessed a using generalized multifactor dimensionality reduction (GMDR) analysis. Additionally, interactions between polygenic risk scores (PRS) and nutrient intake were examined. Results: Low eGFR was associated with higher urinary protein levels (4.67-fold) and correlated with a Western-style diet and with saturated fat, arginine, and isoleucine intakes but not sodium intake. The genetic model for low eGFR included variants linked to energy production and amino acid metabolism, such as rs1047891_CPS1, rs3770636_LRP2, rs5020545_SHROOM3, rs3812036_SLC34A1, and rs4715517_HCRTR2. A high PRS was associated with a 1.78-fold increased risk of low eGFR after adjusting for sociodemographic and lifestyle factors. The PRS from the 6-SNP model interacted with plant-based diets (PBDs) and coffee intake, where individuals with higher PBD and coffee consumption had a lower risk of renal dysfunction. Additionally, CPS1 rs1047891 interacted with vitamin D intake (p = 0.0436), where the risk allele was linked to lower eGFR with low vitamin D intake but not with high intake. Molecular docking showed that vitamin D3 had a lower binding energy to the CPS1 mutant type (−9.9 kcal/mol) than the wild type (−7.5 kcal/mol), supporting a potential gene–nutrient interaction influencing renal function. Conclusions: Middle-aged and elderly individuals with a high genetic risk for renal dysfunction may benefit from a plant-based diet, moderate coffee consumption, and sufficient vitamin D intake. Full article

Background: Vitamin D insufficiency/deficiency is a highly prevalent condition worldwide. At the same time, chronic inflammation is a versatile pathophysiological feature and a common correlate of various disorders, including vitamin D deficiency. Methods: We investigated the possible association of inflammation with 25-hydroxyvitamin D3 (25OHD3) levels and its down-stream pathway by exploring vitamin D-binding protein (DBP) and vitamin D receptor (VDR) genes for single-nucleotide polymorphisms (SNPs), in healthy non-elderly Bahraini adults. Plasma levels of 25OHD3 were measured by chemiluminescence, and six SNPs, four in the GC gene (rs2282679AC, rs4588CA, rs7041GT, and rs2298849TC) and two in the VDR gene (rs731236TC and rs12721377AG) were genotyped by real-time PCR. The concentrations of five inflammatory biomarkers, IL6, IL8, procalcitonin (PCT), TREM1, and uPAR, were measured by ELISA. Results: The results showed no association between the 25OHD3 level and any of the inflammatory markers’ levels. However, three tested SNPs were significantly associated with the concentrations of tested biomarkers except for IL6. The TT mutant genotype of rs2298849TC was associated with lower levels of IL8 and higher levels of PCT and TREM1, the AA mutant genotype of rs2282679AC was associated with decreased levels of IL8 (p ≤ 0.001) and increased levels of TREM1 (p = 0.005), and the GG wild genotype of rs12721377AG was associated with increased levels of 25OHD3 (p = 0.026). Conclusions: Although chronic inflammation is not associated with the vitamin D system in the blood, it is downstream, as revealed by DBP and VDR genotyping. Alternatively, DBP and VDR pursue other functions beyond the vitamin D pathway. Full article

Background: Total hip replacement (THR) significantly improves patients’ quality of life; however, prosthesis loosening remains a significant complication. Vitamin D, essential for calcium homeostasis and bone mineralization, is transported and stabilized by vitamin D binding protein (VDBP). Common single nucleotide polymorphisms (SNPs) in the VDBP gene, rs4588 and rs7041, may influence serum vitamin D levels and potentially impact THR outcomes. This study aimed to analyze the association between these SNPs, serum levels of VDBP and 25(OH)D, and their potential roles in THR outcomes. Methods: The study included three patient groups: (1) patients undergoing arthroscopy after a THR without prosthesis loosening (CA—Control Arthroplasty), (2) patients with hip prosthesis loosening (L—Loosening), and (3) a control group (C—Control). Genotyping of rs4588 and rs7041 in the VDBP gene was conducted using PCR-RFLP and TaqMan Genotyping real-time PCR. Serum levels of VDBP and 25(OH)D were measured using ELISA. Comparisons between groups were performed using statistical analyses, including odds ratios (OR) and significance testing (p-values). Results: There are significant differences in VDBP concentrations between the groups: L vs. CA (p < 0.0001), L vs. C (p = 0.0118), L vs. L + CA (p = 0.0013), CA vs. C (p < 0.0001), and CA vs. L + CA (p < 0.0001), and in 25(OH)D concentrations between groups: L vs. C (p < 0.0001), CA vs. C (p = 0.0008), and C vs. L + CA (p < 0.0001). Conclusions: The study findings suggest a protective role of 25(OH)D against prosthesis loosening in THR. The rs4588 SNP in the VDBP gene may increase the risk of loosening, while differences in VDBP and 25(OH)D concentrations between patient groups highlight their potential importance in THR outcomes. Full article

Recently, we demonstrated that the alopecia observed in vitamin D receptor gene-deficient (Vdr-KO) rats is not seen in rats with a mutant VDR(R270L/H301Q), which lacks ligand-binding ability, suggesting that the ligand-independent action of VDR plays a crucial role in maintaining the hair cycle. Since Vdr-KO rats also showed abnormalities in the skin, the relationship between alopecia and skin abnormalities was examined. To clarify the mechanism of actions of vitamin D and VDR in the skin, protein composition, and gene expression patterns in the skin were compared among Vdr-KO, Vdr-R270L/H301Q, and wild-type (WT) rats. While Vdr-R270L/H301Q rats exhibited normal skin formation similar to WT rats, Vdr-KO rats showed remarkable hyperkeratosis and trans-epidermal water loss in the skin. RNA sequencing and proteomic analysis revealed that the gene and protein expression patterns in Vdr-KO rats significantly differed from those in WT and Vdr-R270L/H301Q rats, with a marked decrease in the expression of factors involved in Shh, Wnt, and Bmp signaling pathways, a dramatic reduction in the expression of hair keratins, and a substantial increase in the expression of epidermal keratins. This study clearly demonstrated that non-liganded VDR is significantly involved in the differentiation, proliferation, and cell death of keratinocytes in hair follicles and the epidermis. Full article