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Life (Basel, Switzerland) Jun 2024The increasing incidence of autoimmune diseases in type 1 diabetes mellitus (T1DM) patients highlights the influence of human leukocyte antigen (HLA) haplotypes on their...
BACKGROUND
The increasing incidence of autoimmune diseases in type 1 diabetes mellitus (T1DM) patients highlights the influence of human leukocyte antigen (HLA) haplotypes on their development. This study aims to determine genetic predisposition to autoimmune diseases in T1DM patients, including thyroid disease and celiac diseases, and explore its correlation with vitamin D deficiency.
METHODS
A cross-sectional study involving thirty-six T1DM children was conducted. Typing was performed for the HLA A, B, C, DP, DR, and DQ loci. Regression analysis linked DR-DQ haplotypes to T1DM and the associated conditions.
RESULTS
The most frequent predisposing alleles and haplotypes were HLA-DR3 (70.27%), DQ2 (70.27%), DR3-DQ2 (70.27%), DQB1*02:01 (70.27%), A02 (54.05%), whereas the most prevalent protecting allele was DPB1*04:01 (52.63%). Positive correlations were observed between positive anti-thyroid peroxidase antibodies and the absence of protective alleles (DPB1*04:02, = 0.036; DPB1*04:01, = 0.002). Associations were found between the absence of DPB1*04:01 and anti-thyroglobulin antibodies ( = 0.03). HLA allele DPB1*03:01 was linked with vitamin D deficiency ( = 0.021). Positive anti-transglutaminase antibodies correlated with C03:03 ( = 0.026) and DRB1*04:01-DQA1*03-DQB1*03:01 ( < 0.0001) and the lack of DQA1*01:03-DQB1*06:03-DRB1*13:01 ( < 0.0001).
CONCLUSIONS
The predisposing T1DM haplotypes were associated with the presence of anti-transglutaminase and anti-thyroid antibodies, indicating a genetic predisposition to autoimmune diseases.
PubMed: 38929763
DOI: 10.3390/life14060781 -
Life (Basel, Switzerland) May 2024Maternal-fetal gestational pathology is one of the biggest challenges in the field of health at this moment. The current study is designed to determine the effects of...
BACKGROUND AND OBJECTIVES
Maternal-fetal gestational pathology is one of the biggest challenges in the field of health at this moment. The current study is designed to determine the effects of vitamin D on pregnancy, starting with the idea that impairment of vitamin D status is thought to be correlated with impairment of the newborn's health.
MATERIALS AND METHODS
In this retrospective study, we tried to establish the link between vitamin D deficiency and maternal characteristics and also how it impacted the clinical status of the newborn. We analyzed a group of 260 patients: 130 pregnant women and 130 newborns, in whom vitamin D status was detected using the serum levels of 25-hydroxyvitamin D (25-(OH)D).
RESULTS
The results showed that vitamin D deficiency has a high incidence among pregnant women, as was presented in many important international studies. Our study also showed a positive, direct correlation between the mother's and newborn's vitamin D status.
CONCLUSIONS
Taking into consideration that vitamin D deficiency has been correlated with many complications, both in maternal and newborn health, a serum level determination of 25-(OH)D is necessary in the first trimester of pregnancy, and after that, adequate supplementation is necessary in order to prevent any negative effects.
PubMed: 38929697
DOI: 10.3390/life14060714 -
Medicina (Kaunas, Lithuania) Jun 2024I propose that a deficiency of essential fatty acids (EFAs) and an alteration in their (EFAs) metabolism could be a major factor in the pathogenesis of sepsis and... (Review)
Review
I propose that a deficiency of essential fatty acids (EFAs) and an alteration in their (EFAs) metabolism could be a major factor in the pathogenesis of sepsis and sepsis-related mortality. The failure of corticosteroids, anti-TNF-α, and anti-interleukin-6 monoclonal antibodies can be attributed to this altered EFA metabolism in sepsis. Vitamin C; folic acid; and vitamin B1, B6, and B12 serve as co-factors necessary for the activity of desaturase enzymes that are the rate-limiting steps in the metabolism of EFAs. The altered metabolism of EFAs results in an imbalance in the production and activities of pro- and anti-inflammatory eicosanoids and cytokines resulting in both hyperimmune and hypoimmune responses seen in sepsis. This implies that restoring the metabolism of EFAs to normal may form a newer therapeutic approach both in the prevention and management of sepsis and other critical illnesses.
Topics: Humans; Sepsis; Fatty Acids, Essential
PubMed: 38929553
DOI: 10.3390/medicina60060934 -
Animals : An Open Access Journal From... Jun 2024Nutritional secondary hyperparathyroidism (NSH) in dogs is a condition that develops in response to a vitamin D deficiency or an imbalanced calcium-to-phosphorus ratio...
Nutritional secondary hyperparathyroidism (NSH) in dogs is a condition that develops in response to a vitamin D deficiency or an imbalanced calcium-to-phosphorus ratio in dog food. Puppies of large-breed dogs exclusively fed a non-supplemented, boneless raw meat diet are especially susceptible to developing NSH due to their elevated calcium requirement. Reports on NSH in companion animals have been sparse in the last decades due to dog owners having easy access to commercially balanced dog foods. However, with the rising popularity of meat-based raw feeding, this condition has re-emerged. In this case series, four large-breed puppies fed exclusively non-supplemented, boneless raw meat diets presented with complaints of acute onset of pain and paresis. Radiographs and/or computed tomography (CT) scans showed reduced radio density of the skeleton in all four puppies. Two of the dogs had pathological fractures, and these two puppies were euthanized. One was subjected to a post mortem examination, which revealed cortical bone resorption and hypertrophy of the parathyroid glands. The remaining two puppies rapidly improved after receiving pain medication and a commercial, balanced diet. This case series demonstrates a risk of young dogs developing severe neurological deficits when fed a non-supplemented, boneless raw meat diet.
PubMed: 38929402
DOI: 10.3390/ani14121783 -
Children (Basel, Switzerland) May 2024The double burden of malnutrition (DBM) is a condition in which malnutrition coexists with overweight, reflecting a new layer of malnutrition. Our objectives were to...
The double burden of malnutrition (DBM) is a condition in which malnutrition coexists with overweight, reflecting a new layer of malnutrition. Our objectives were to assess prevalence; test associations between DBM and 24-hour movement behaviors; and investigate whether DBM is associated with clusters of social determinants. Methods: This multicenter cross-sectional study included 1152 adolescents (12 to 17 years old) from four Brazilian cities. Body mass index (BMI, kg/m) was used to estimate overweight, and the adopted cutoff points took into account the curves established for age and sex: Z-score > 1 and ≤2 (overweight) and Z-score > 2 (obesity). The serum concentration of 25-hydroxyvitamin D [25(OH)D] was stratified into three levels: vitamin D deficiency ≤ 20 ng/mL; vitamin D insufficiency = 21-29 ng/mL; optimal vitamin D ≥ 30 ng/mL. We used multilevel Poisson regression models to estimate prevalence ratios (PRs) and their respective 95% confidence intervals (95%CI) and to analyze the association between DBM and covariates. A significance level of < 0.05 was considered. Cluster analyses were performed by applying a combination of hierarchical and non-hierarchical methods. Results: A population prevalence of DBM of 7.3% (95% CI: 5.9-8.9) was revealed. A percentage of 19.2% (95% CI: 17.0-21.6) of adolescents were overweight, and 8.3% (95% CI: 6.8-10.1) were obese. A total of 41.5% (95% CI: 38.7-44.4) had vitamin D deficiency, and 25.8% (95% CI: 23.4-28.4) had vitamin D insufficiency. However, 24-hour movement behaviors were not associated with DBM. Adolescents living in the southern region of the country, from public schools whose mothers have higher education, have a 1.94 [PR = 2.94 (95% CI: 1.20-7.23)] times greater chance of developing DBM. These results highlight the importance of specific factors to improve the nutritional health of adolescents, considering the specific social determinants identified in this study.
PubMed: 38929200
DOI: 10.3390/children11060620 -
International Journal of Molecular... Jun 2024Lung cancer has an unfavorable prognosis with a rate of low overall survival, caused by the difficulty of diagnosis in the early stages and resistance to therapy. In... (Review)
Review
Lung cancer has an unfavorable prognosis with a rate of low overall survival, caused by the difficulty of diagnosis in the early stages and resistance to therapy. In recent years, there have been new therapies that use specific molecular targets and are effective in increasing the survival chances of advanced cancer. Therefore, it is necessary to find more specific biomarkers that can identify early changes in carcinogenesis and allow the earliest possible treatment. Vitamin D (VD) plays an important role in immunity and carcinogenesis. Furthermore, the vitamin D receptor (VDR) regulates the expression of various genes involved in the physiological functions of the human organism. The genes encoding the VDR are extremely polymorphic and vary greatly between human populations. To date, there are significant associations between VDR polymorphism and several types of cancer, but the data on the involvement of VDR polymorphism in lung cancer are still conflicting. Therefore, in this review, our aim was to investigate the relationship between VDR single-nucleotide polymorphisms in humans and the degree of risk for developing lung cancer. The studies showcased different gene polymorphisms to be associated with an increased risk of lung cancer: , , , , and . In addition, there is a strong positive correlation between VD deficiency and lung cancer development. Still, due to a lack of awareness, the assessment of VD status and VDR polymorphism is rarely considered for the prediction of lung cancer evolution and their clinical applicability, despite the fact that studies have shown the highest risk for lung cancer given by TaqI gene polymorphisms and that VDR polymorphisms are associated with more aggressive cancer evolution.
Topics: Humans; Receptors, Calcitriol; Lung Neoplasms; Vitamin D; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Risk Factors
PubMed: 38928369
DOI: 10.3390/ijms25126664 -
International Journal of Molecular... Jun 2024Biotin (vitamin B7, or vitamin H) is a water-soluble B-vitamin that functions as a cofactor for carboxylases, i.e., enzymes involved in the cellular metabolism of fatty... (Review)
Review
Biotin (vitamin B7, or vitamin H) is a water-soluble B-vitamin that functions as a cofactor for carboxylases, i.e., enzymes involved in the cellular metabolism of fatty acids and amino acids and in gluconeogenesis; moreover, as reported, biotin may be involved in gene regulation. Biotin is not synthesized by human cells, but it is found in food and is also produced by intestinal bacteria. Biotin status/homeostasis in human individuals depends on several factors, including efficiency/deficiency of the enzymes involved in biotin recycling within the human organism (biotinidase, holocarboxylase synthetase), and/or effectiveness of intestinal uptake, which is mainly accomplished through the sodium-dependent multivitamin transporter. In the last years, administration of biotin at high/"pharmacological" doses has been proposed to treat specific defects/deficiencies and human disorders, exhibiting mainly neurological and/or dermatological symptoms and including biotinidase deficiency, holocarboxylase synthetase deficiency, and biotin-thiamine-responsive basal ganglia disease. On the other hand, according to warnings of the Food and Drug Administration, USA, high biotin levels can affect clinical biotin-(strept)avidin assays and thus lead to false results during quantification of critical biomarkers. In this review article, recent findings/advancements that may offer new insight in the abovementioned research fields concerning biotin will be presented and briefly discussed.
Topics: Humans; Biotin; Homeostasis; Biotinidase Deficiency; Biotinidase; Holocarboxylase Synthetase Deficiency; Carbon-Nitrogen Ligases; Animals; Ataxia; Basal Ganglia Diseases
PubMed: 38928282
DOI: 10.3390/ijms25126578 -
International Journal of Molecular... Jun 2024The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes...
The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60-35.40) vs. 22.95 mg/dL (17.60-33.30), = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678-1.189; = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG-33.8%, GA-50.2%, and AA-16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure ( = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.
Topics: Humans; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Kidney Transplantation; Male; Female; Cardiovascular Diseases; Middle Aged; Polymorphism, Single Nucleotide; Adult; Risk Factors; Genetic Predisposition to Disease; Genotype; Immunosuppressive Agents; Cyclosporine; Tacrolimus
PubMed: 38928269
DOI: 10.3390/ijms25126562 -
International Journal of Molecular... Jun 2024We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced... (Review)
Review
Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, Gene-Related Tumors, and Insulin Resistance.
We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P ( = 9 studies, N = 1375) involved as a starting point parathyroid NETs ( = 7) or pancreatitis ( = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies ( = 7) included MEN1-related insulinomas ( = 2) or MEN1-associated PHP ( = 2) or analyses of genetic profile ( = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified ( = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome ( = 1). Normocalcemic and mildly symptomatic hyperparathyroidism ( = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.
Topics: Humans; Hyperparathyroidism, Primary; Insulin Resistance; Hypercalcemia; Pancreatitis; Female; Male; Proto-Oncogene Proteins; Pancreatic Neoplasms; Multiple Endocrine Neoplasia Type 1; Parathyroid Neoplasms; Adult; Parathyroidectomy; Neuroendocrine Tumors; Pancreas
PubMed: 38928056
DOI: 10.3390/ijms25126349 -
International Journal of Molecular... Jun 2024Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary...
Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken. Our hypothesis was that the levels of vitamin D and its active metabolite would be associated with CVRPs comparably in women with and without PCOS. In women with PCOS ( = 29) and controls ( = 29), 54 CVRPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D (25(OH)D) and the active 1,25-dihydroxyvitamin D (1,25(OH)D) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had comparable IR and systemic inflammation (normal C-reactive protein) to control women, though had higher free androgen index and anti-Mullerian hormone levels. 25(OH)D and 1,25(OH)D levels did not differ between groups. Nine CVRPs were higher in PCOS ( < 0.05) (Galectin-9, Brother of CDO, C-motif chemokine 3, Interleukin-18 receptor-1, Thrombopoietin, Interleukin-1 receptor antagonist protein, Programmed cell death 1 ligand-2, Low-affinity immunoglobulin gamma Fc-region receptor II-b and human growth hormone), whilst 45 CVRPs did not differ. 25(OH)D correlated with five CVRPs in PCOS and one in controls ( < 0.05). Despite the women with PCOS not exhibiting overt systemic inflammation, 9 of 54 CVRPs were elevated, all relating to inflammation, and 5 of these correlated with 25(OH)D suggesting an ongoing underlying inflammatory process in PCOS even in the absence of obesity/IR.
Topics: Humans; Polycystic Ovary Syndrome; Female; Adult; Cross-Sectional Studies; Biomarkers; Vitamin D; Cardiovascular Diseases; Heart Disease Risk Factors; Vitamin D Deficiency; Insulin Resistance; Obesity; Young Adult
PubMed: 38928037
DOI: 10.3390/ijms25126330