Magnesium research最新文献

Epidemiological outburst of type 2 diabetes is of great global concern. T2D starts with Insulin Resistance (IR) which arises largely due to environmental factors and to a lesser extent due to genetic factor. IR gradually develops into T2D and encompasses a wide array of conditions including Impaired Glucose Tolerance (IGT), hyperinsulinemia, Impaired Fasting Glucose (IFG), and Impaired Insulin Release (IIR). Initiation of IR increases the risk of Cardiovascular Diseases (CVD). Therefore, early diagnosis and management of IR and its related outcomes (hyperinsulinemia, hyperglycemia, and dyslipidemia) should be the prime focus of intervention therapies. Present research aimed to evaluate the synergistic combination of Magnesium orotate (MOD), Menaquinone- 7 (MK-7), and Cholecalciferol (CHOL) for the management of these therapeutic targets in the Streptozotocin-Nicotinamide-induced T2D Wistar rat model. Synergistic combination was found to be superior over its individual components in management of hyperglycemia, impaired insulin secretion, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and dyslipidemia (p < 0.01 or p < 0.05). Its effect was found to be equivalent or better than reference drugs (p < 0.01 or p < 0.05). Histopathological analysis depicted that combination treatment was able to regenerate and preserve pancreatic β-cell mass in diabetic rats. In conclusion, combination studied in present research can be evaluated further under clinical settings for management of IR and its related outcomes.

No-reflow phenomenon is a serious complication of percutaneous coronary intervention. Magnesium may play a role in pathogenesis of no-reflow phenomenon since it interacts with processes like platelet inhibition and endothelial-dependent vasodilatation. Relationship of serum magnesium concentration at admission and angiographic no-reflow phenomenon in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is investigated in the present study. A total of 2.248 consecutive patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention were analyzed. After reopening of the infarct related artery, a TIMI flow rate ≤ 2 was defined as no-reflow. No-reflow phenomenon developed in 386 (17.1 %) patients. Serum magnesium concentration was significantly lower in no-reflow group (1.87 ± 0.25 vs. 2.07 ± 0.33 mg/dL, p<0.001). ROC curve analysis showed that Mg at a cut-point of 1.92 has 71.4% sensitivity and 75.2% specificity in detecting no-reflow phenomenon. In multivariate logistic regression analysis, age, serum magnesium concentration, and stent length were found as independent predictors of no-reflow phenomenon. Serum magnesium concentration is associated with no-reflow phenomenon in ST elevation myocardial infarction patients who underwent primary PCI.

While magnesium deficiency is common and its effects well known on the nervous system, very few studies has been dedicated to the efficiency of magnesium replacement treatments on the central nervous system. In this study, the effects of oral administration of magnesium salts of acetyl-taurinate on the central manifestations of magnesium deficiency is described in rats submitted to low-magnesium diet and in a murine model of Alzheimer's disease. We tested the effect of ATA Mg^®, a salt combining magnesium and taurine, on the hippocampus, a critical component of cognition. 7-10-month-old rats were submitted to dietary magnesium deprivation for 64 days. The effect of magnesium deficiency was studied in ex vivo hippocampal slices. We showed that long-term potentiation of synaptic transmission in the hippocampus was significantly improved by the oral administration of ATA Mg^® at a dose of 50 mg/kg bw/day, which is comparable to the recommended dose in humans. 7-10-months-old transgenic APP/PS1 mice, a model of Alzheimer's disease, received ATA Mg^® during 24 days at a dose of 700 mg/kg bw/day which is the dose used in previous studies demonstrating the positive effect of magnesium supplementation. We showed that long-term potentiation was significantly improved in the treated mice. Moreover, the expression of NR2B subunit of NMDA receptors, known to be involved in synaptic plasticity, was significantly increased in the hippocampus. These results demonstrate the ability of ATA Mg^® to improve the symptoms related to chronic magnesium deficiency at the level of the hippocampus suggesting its bioavailability and effectiveness in reaching the central nervous system.

Hypomagnesemia and hypermagnesemia could have serious implications and possibly lead to progress from a mild form to a severe outcome of Covid-19. Susceptibility of subjects with low magnesium status to develop and enhance this infection is possible. There is little data on the magnesium status of patients with Covid-19 with different degrees of severity. This study was conducted to evaluate prevalence of dysmagnesemia in a prospective Covid-19 cohort study according to the severity of the clinical manifestations and to identify factors associated. Serum magnesium was measured in 300 of 549 patients admitted to the hospital due to severe Covid-19. According to the WHO guidelines, patients were classified as moderate, severe, or critical. 48% patients had a magnesemia below 0.75 mmol/L (defined as magnesium deficiency) including 13% with a marked hypomagnesemia (<0.65 mmol/L). 9.6% had values equal to or higher than 0.95 mmol/L. Serum magnesium concentrations were significantly lower in female than in male (0.73 ± 0.12 vs 0.80 ± 0.13 mmol/L), whereas the sex ratio M/F was higher in severe and critical form (p<0.001). In a bivariate analysis, the risk of magnesium deficiency was significantly and negatively associated with infection severity (p<0.001), sex ratio (M/F, p<0.001), oxygenotherapy (p<0.001), stay in critical care unit (p=0.028), and positively with nephropathy (p=0.026). Logistic regression analysis revealed that the strongest predictors of magnesium deficiency were female sex (OR=2.67, p<0.001) and nephropathy (OR=2.12, p=0.032) and after exclusion of sex ratio, the severity of infection (OR=0.46, p=0.04 and OR=0.39 p=0.01), for critical and moderate forms, respectively. This transversal study reveals a high prevalence of hypomagnesemia in hospitalized patients for Covid-19, while high-level serum magnesium concentration was more prevalent in critical form.

Primary findings from a recent study reported that magnesium supplementation significantly reduced stress in severely stressed subjects with low magnesemia, and additional vitamin B6 enhanced this effect. The mechanism by which combining magnesium and vitamin B6 leads to reduced stress in these subjects remains to be elucidated. This secondary analysis investigated the impact of magnesium and vitamin B6 supplementation and perceived stress on erythrocyte magnesium levels, as a marker of body magnesium status. This was a secondary analysis from an 8-week randomized controlled trial comparing oral magnesium (300 mg) and magnesium-vitamin B6 (300 mg + 30 mg) supplementation. Stress level and erythrocyte magnesium level at baseline, and change in erythrocyte magnesium and serum vitamin B6 levels at weeks 4 and 8, were analyzed. Overall, 264 subjects were randomized to treatment and had evaluable Depression Anxiety Stress Scale scores (132 in each treatment arm). At baseline, stress scores, and mean serum magnesium, erythrocyte magnesium, and serum vitamin B6 concentrations were similar between arms. Although not significant between groups, a significant increase over time in erythrocyte magnesium levels was observed in the subgroup of subjects with low baseline erythrocyte magnesium levels (<1.6 mmol/L) following treatment with magnesium and magnesium-vitamin B6 (week 4:0.21 mmol/L [95% confidence interval (CI), 0.10 to 0.31], p = 0.0003; and 0.13 mmol/L [95% CI, 0.02 to 0.23], p = 0.0233, respectively). Change from baseline in circulating vitamin B6 levels at weeks 4 and 8 in the magnesium-vitamin B6 supplemented group (314.96 nmol/L [95%CI, 294.61 to 335.31]) was significantly different (p < 0.0001) compared with the magnesium supplemented group (-0.39 nmol/L [95% CI, -20.73 to 19.94]). Magnesium alone and magnesium-vitamin B6 provided statistically significant increases in erythrocyte magnesium in subjects with low magnesium status (<1.6mmol/L). Vitamin B6 supplementation did not further increase magnesium levels.

Magnesium transporter 1 (MAGT1) is a key protein that regulates the level of free Mg²⁺ in cells. Previous studies found that the downregulation of MAGT1 expression in CD8⁺T cells of HBV patients was correlated with the decrease of intracellular magnesium. However, the expression of MAGT1 mRNA in the CD8⁺T cells from HBV patients was not significantly altered, indicating that the change in MAGT1 expression was accomplished through posttranscriptional regulation. Through bioinformatics and qRT-PCR detection, miR-199a-5p was found to have a target gene relationship with MAGT1. The expression levels of miR-199a-5p and MAGT1 in HBV infection were evaluated. Lentivirus assays were used to analyze the effects of miR-199a-5p upregulation and downregulation on the MAGT1 expression level and the immune system. Results showed no significant change in the expression of MAGT1 mRNA in HBV-infected cell lines, but the expression of MAGT1 was downregulated. Additionally, the expression level of miR-199a-5p was significantly increased. To this end, we predicted a target relationship between miR-199a-5p and MAGT1 by using TargetScan and verified this relationship through a luciferase activity reporter gene assay. As a result, MAGT1 was found to be the direct target of miR-199a-5p. The targeted inhibition of MAGT1 induced by miR-199a-5p overexpression led to the immune function depletion of CD8⁺T cells in HBV patients. Downregulating the expression level of miR-199a-5p could effectively improve the functional depletion of CD8⁺T cells. These findings indicate that miR-199a-5p and MAGT1 could potentially be used as biomarkers for the diagnosis and treatment of chronic HBV infection.

Magnesium (Mg) plays important roles in maintaining genomic stability and cellular redox. Mg also serves as nature's physiological calcium (Ca) channel antagonist, controlling intracellular Ca entry. Because Ca is the most important second messenger, its intracellular concentration is tightly regulated. Excess intracellular Ca can activate aberrant signaling pathways leading to the acquisition of pathological characteristics and cell injury. Several epidemiological studies have linked Mg deficiency (MgD) and increased Ca:Mg ratios with higher incidences of colon cancer and increased mortality. While it is estimated that less than 50% of the US population consumes the recommended daily allowance for Mg, Ca supplementation is widespread. Therefore, we studied the effect of MgD, with variable Ca:Mg ratios on cellular oxidative stress, cell migration, calpain activity, and associated signaling pathways using the CT26 colon cancer cell line. MgD (with Ca:Mg ratios >1) elevated intracellular Ca levels, calpain activity and TRPM7 expression, as well as oxidative stress and cell migration, consistent with observed degradation of full-length E-cadherin, β-catenin, and N-terminal FAK. MgD was accompanied by enhanced degradation of IκBα and the transactivation domain containing the C-terminus of NF-κB p65 (RelA). MgD-exposed CT26 cells exhibited increased p53 degradation and aneuploidy, markers of genomic instability. By contrast, these pathological changes were not observed when CT26 were cultured under MgD conditions where the Ca:Mg ratio was kept at 1. Together, these data support that exposure of colon cancer cells to MgD with physiological Ca concentrations (or increasing Ca:Mg ratios) leads to the acquisition of a more aggressive, metastatic phenotype.

Beside routinely used 0.5 mmol/L dialysate-magnesium, higher dialysate-magnesium (1.0 mmol/L) was recently introduced. The aim of this study was to evaluate the impact of different dialysate-magnesium on serum and intraerythrocyte levels of magnesium (Mg) before and after dialysis. The study included 43 patients receiving chronic hemodialysis, divided into two groups based on dialysate-magnesium (0.5 or 1.0 mmol/L) used prior to study initiation and during 12 months of follow-up. Blood samples were taken at the mid-week dialysis; total serum Mg was measured colorimetrically and intraerythrocyte Mg by atomic absorption spectrophotometry. Hypermagnesiemia-associated complications were observed for 12 months. Total serum Mg was 1.14 ± 0.19 mmol/L before and 0.95 ± 0.16 mmol/L after dialysis in patients using lower dialysate-Mg (p < 0.001), whereas it was 1.47 ± 0.25 mmol/L before and 1.49 ± 0.18 mmol/L after dialysis in patients using higher dialysate-Mg (p = 0.926). Intraerythrocyte Mg was 1.98 ± 0.34 mmol/L before and 1.97 ± 0.28 mmol/L after dialysis in the lower dialysate-Mg group (p = 0.939), while it was 2.09 ± 0.37 mmol/L before and 2.19 ± 0.48 mmol/L after dialysis in the higher dialysate group (p = 0.067). After 12 months total serum Mg decreased in both the groups, remaining lower in 0.5 mmol/L dialysate-Mg group. No hypermagnesiemia-related symptoms occur during 12 months of follow-up in both the groups. In patients using lower dialysate-Mg total serum Mg remains within the reference range and shows postdialytic decline, while in higher dialysate-Mg group it exceeded reference range before and after dialysis without significant intradialytic change. The intraerythrocyte values remain within reference range with both dialysates used. No clinical signs and symptoms of hypermagnesiemia occur during longer administration of higher dialysate-magnesium despite high total serum Mg level.