Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

Wilson disease a rare autosomal recessive inherited disorder of copper metabolism, is characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson disease is often fatal if it is not recognized early and treated when it is symptomatic. Gitelman syndrome is also an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. Hereditary sensory autonomic neuropathy type IV (HSAN-IV), a very rare condition that presents in infancy, is characterized by anhidrosis, absence of pain sensation, and self-mutilation. It is usually accompanied by developmental delay and mental retardation. We report a case of Wilson disease manifested as fulminant hepatitis, acute pancreatitis, and acute kidney injury in a 15-year-old boy comorbid with HSAN-IV and Gitelman syndrome. Such concurrence of three genetic diseases is an extremely rare case.
Acute Kidney Injury ; Adolescent ; Brain ; Calcium ; Copper ; Genes, Recessive ; Gitelman Syndrome ; Hepatitis ; Hepatolenticular Degeneration ; Humans ; Hydrogen-Ion Concentration ; Hypohidrosis ; Intellectual Disability ; Kidney ; Liver ; Magnesium ; Male ; Metabolism ; Pancreatitis ; Potassium ; Sensation

Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg-free artificial cerebrospinal fluid (ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg-free ACSF for 10 min-20 min, synchronous recurrent seizure-like events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges (IIDs) to pre-ictal epileptiform discharges (PIDs), and then to IDs. During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 μmol/L of the GABA receptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 μmol/L muscimol abolished all the epileptiform discharges. When the GABA receptor antagonist bicuculline was applied at 10 μmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.
Animals ; Animals, Newborn ; Bicuculline ; pharmacology ; Disease Models, Animal ; Epilepsy ; pathology ; GABA-A Receptor Agonists ; pharmacology ; GABA-A Receptor Antagonists ; therapeutic use ; Hippocampus ; drug effects ; metabolism ; physiopathology ; In Vitro Techniques ; Magnesium ; metabolism ; pharmacology ; Male ; Membrane Potentials ; drug effects ; Mice ; Mice, Inbred C57BL ; Muscimol ; pharmacology ; Nerve Net ; drug effects ; Receptors, GABA-A ; metabolism

Metal binding proteins or metallo-proteins are important for the stability of the protein and also serve as co-factors in various functions like controlling metabolism, regulating signal transport, and metal homeostasis. In structural genomics, prediction of metal binding proteins help in the selection of suitable growth medium for overexpression’s studies and also help in obtaining the functional protein. Computational prediction using machine learning approach has been widely used in various fields of bioinformatics based on the fact all the information contains in amino acid sequence. In this study, random forest machine learning prediction systems were deployed with simplified amino acid for prediction of individual major metal ion binding sites like copper, calcium, cobalt, iron, magnesium, manganese, nickel, and zinc.
Amino Acid Sequence* ; Binding Sites* ; Calcium ; Carrier Proteins ; Cobalt ; Computational Biology ; Copper ; Forests* ; Genomics ; Homeostasis ; Iron ; Machine Learning ; Magnesium ; Manganese ; Metabolism ; Nickel ; Zinc

OBJECTIVE: Serum parameters of calcium homeostasis were measured based on previously published evidence linking osteoporotic fractures and/or bone/mineral loss with antipsychotics. METHODS: Prospective, four-week, time-series trial was conducted and study population consisted of patients of both genders, aged 35-85 years, admitted within the routine practice, with acute psychotic symptoms, to whom an antipsychotic drug was either introduced or substituted. Serial measurements of serum calcium, phosphorous, magnesium, 25(OH)D, parathyroid hormone, calcitonin, osteocalcin and C-telopeptide were made from patient venous blood samples. RESULTS: Calcium serum concentrations significantly decreased from baseline to the fourth week (2.42+/-0.12 vs. 2.33+/-0.16 mmol/L, p=0.022, n=25). The mean of all calcemia changes from the baseline was -2.6+/-5.7% (-24.1 to 7.7) with more decreases than increases (78 vs. 49, p=0.010) and more patents having negative sum of calcemia changes from baseline (n=28) than positive ones (n=10) (p=0.004). There were simultaneous falls of calcium and magnesium from baseline (63/15 vs. 23/26, p<0.001; OR=4.75, 95% CI 2.14-10.51), phosphorous (45/33 vs. 9/40, p<0.001; 6.06, 2.59-14.20) and 25(OH)D concentrations (57/21 vs. 13/35, p<0.001; 7.31, 3.25-16.42), respectively. Calcemia positively correlated with magnesemia, phosphatemia and 25(OH)D values. Parathyroid hormone and C-telopeptide showed only subtle oscillations of their absolute concentrations or changes from baseline; calcitonin and osteocalcin did not change. Adjustment of final calcemia trend (depletion/accumulation) for relevant risk factors, generally, did not change the results. CONCLUSION: In patients with psychotic disorders and several risks for bone metabolism disturbances antipsychotic treatment was associated with the decrease of calcemia and changes in levels of the associated ions.
Antipsychotic Agents* ; Blood Chemical Analysis ; Bone and Bones ; Calcitonin ; Calcium* ; Homeostasis ; Humans ; Ions ; Magnesium ; Metabolism* ; Minerals ; Osteocalcin ; Osteoporotic Fractures ; Parathyroid Hormone ; Prospective Studies ; Psychotic Disorders ; Risk Factors

OBJECTIVETo observe the effect of magnesium sulfate, Nifedipine Tablet (NT) combined Salvia Injection (SI) on endothelin-1 (ET-1), nitric oxide (NO), thromboxane A2(TXA2), prostacyclin I2(PG2), and hemorheology of preeclampsia patients.

METHODSTotally 704 preeclampsia patients were randomly assigned to the treatment group and the control group, 352 cases in each group. All patients were treated with magnesium sulfate combined NT (on the first day: slow intravenous injection of magnesium sulfate 5 g + intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg; on the second and third day, intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg), while those in the treatment group were dripped with SI additionally at 20 mL per day for 3 consecutive days. Before and after treatment plasma levels of endothelin-1 (ET-1), nitric oxide (NO), TXA2, PGi2, and hemorheology indicators [such as high blood viscosity (HBV), low blood viscosity (LBV), plasma viscosity (PV), erythrocyte rigidity index (ERI), fibrinogen (FIB)] of two groups were detected.

RESULTSCompared with the same group before treatment, serum levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the two groups after treatment (P <0. 05), but levels of NO and PG2 increased (P <0. 05). Compared with the control group in the same period, levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the treatment group after treatment (P <0. 05), but levels of NO and PGI2 increased (P <0. 05).

CONCLUSIONMagnesium sulfate, NT combined SI could effectively regulate the balance of ET-1/NO and TXA2/PGI2, and improve hemorheology of preeclampsia patients.

Drug Therapy, Combination ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelin-1 ; metabolism ; Epoprostenol ; metabolism ; Female ; Hemorheology ; Humans ; Injections ; Magnesium Sulfate ; administration & dosage ; pharmacology ; therapeutic use ; Nifedipine ; administration & dosage ; pharmacology ; therapeutic use ; Nitric Oxide ; metabolism ; Pre-Eclampsia ; drug therapy ; Pregnancy ; Salvia ; Tablets ; Thromboxane A2 ; metabolism

OBJECTIVETo summarize the importance of Mediterranean diet in the prevention and management of type 2 diabetes.

DATA SOURCESWe searched electronic database on PubMed up to 14 April 2014, we identified these articles with following key words: "Mediterranean diet" and "diabetes". The initial search resulted in 451 entries. The search strategy had no language and publication date restrictions. The relevance of the studies was assessed based only on the title and abstract. The studies included in our review had to match the following inclusion criteria: (1) randomized clinical trials and meta-analysis or systematic review, and (2) provided strong evidence for the diet as a way to prevent type 2 diabetes, and improve glycemic control and cardiovascular risk factors in diabetic patients. We reviewed 49 manuscripts and only 22 met our inclusion criteria.

STUDY SELECTIONRelevant literatures including randomized control trials, meta-analysis or systematic review.

RESULTSBased on several studies, Mediterranean diet is inversely related to type 2 diabetes and plays important roles in the management of type 2 diabetes. Based on the evidence gathered and evaluated from various studies, we concluded combination and interaction of Mediterranean diet components, such as fruits, vegetables, nuts, legumes, whole grains, fish and moderate intakes of red wine, which contain essential nutrients and health promoting properties, including high fibers, high magnesium, high anti-oxidant and high monounsaturatal fatty acids (MUFA). Interaction and combination of these essential nutrients and health promoting properties found to lower body weight, hemoglobin A1C (HbA1c), low density lipoprotein (LDL), oxidative-stress and improve high density lipoprotein (HDL) level; which are beneficial for prevention and prognosis improvement of type 2 diabetes.

CONCLUSIONSIn the modern society, poor dietary habits accompanied by inadequate physical activity are associated with the risk of having obesity and type 2 diabetes. Promoting healthy lifestyle and diet are not only beneficial in the prevention and treatment of various diseases but also important in maintaining the overall health. Switching from unhealthy diet to health-friendly diet such as Mediterranean diet represents healthy lifestyle choice.

Antioxidants ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; prevention & control ; Diet, Mediterranean ; Fatty Acids, Monounsaturated ; metabolism ; Humans ; Magnesium ; metabolism

OBJECTIVETo investigate the tissue toxicity and degradation of ZK60 magnesium alloy with micro-arc oxidation coatings (MAO-ZK60), in order to discuss the possibility of its potential application for orthopedic implantation.

METHODSEighteen Sprague-Dawley rats were randomized equally to three groups of A, B, C. MAO-ZK60 sticks were implanted in the femoral condyles of rats in group A (experimental group). Sticks of ZK60 magnesium alloy without any surface treatment (ZK60) were implanted in the femoral condyles of rats in group B (control group). The poly L-lactic acid (PLLA) sticks were implanted in the femoral condyles of rats in group C (control group). The changes of blood bio-chemical indexes of different groups were observed and compared. All the rats were sacrificed at 12 weeks and histological observation of liver and kidney were carried out to evaluate the hepatic and renal toxicity. Micro-CT was used to evaluate the degradation of the implants and to observe the bone-implant interface. GEHC MicroView software was operated to calculate the volume variation of magnesium alloy.

RESULTSThere was no apparent biochemical index change with time in each group, and there was no significant change among each group. No significant pathology change of liver and kidney was detected among three groups. By using a micro-CT, a gap was found on the bone-implant interface at 4 weeks after implantation in group A, which decreased gradually at 8 weeks after implantation and continued to decrease at 12 weeks after implantation. A good combination between bone and implant formed at 12 weeks after implantation. Group A has less change of volume with time than group B (P < 0.05).

CONCLUSIONZK60 magnesium alloy with micro-arc oxidation coatings is safe in vivo. It has higher corrosion resistance than ZK60 magnesium alloy without any surface treatment.

Alloys ; chemistry ; metabolism ; toxicity ; Animals ; Magnesium ; chemistry ; Male ; Rats ; Rats, Sprague-Dawley

Clinical studies reported hypomagnesaemia in long-term omeprazole usage that was probably due to intestinal Mg2+ wasting. Our previous report demonstrated the inhibitory effect of omeprazole on passive Mg2+ transport across Caco-2 monolayers. The present study aimed to identify the underlying mechanism of omeprazole suppression of passive Mg2+ absorption. By using Caco-2 monolayers, we demonstrated a potent inhibitory effect of omeprazole on passive Mg2+, but not Ca2+, transport across Caco-2 monolayers. Omeprazole shifted the %maximum passive Mg2+ transport-Mg2+ concentration curves to the right, and increased the half maximal effective concentration of those dose-response curves, indicating a lower Mg2+ affinity of the paracellular channel. By continually monitoring the apical pH, we showed that omeprazole suppressed apical acid accumulation. Neomycin and spermine had no effect on passive Mg2+ transport of either control or omeprazole treated monolayers, indicating that omeprazole suppressed passive Mg2+ transport in a calcium sensing receptor (CaSR)-independent manner. The results of western blot analysis showed that omeprazole significantly suppressed claudin (Cldn)-7 and -12, but not Cldn-2, expression in Caco-2 cells. By using apical solution of pH 5.5, 6.0, 6.5, and 7.0, we found that apical acidity markedly increased passive Mg2+ transport, Mg2+ affinity of the paracellular channel, and Cldn-7 and -12 expression in Caco-2 monolayers. Apical acidity abolished the inhibitory effect of omeprazole on passive Mg2+ transport and Cldn-7 and -12 expression. Our results provided the evidence for the regulation of intestinal passive Mg2+ absorption by luminal acidity-induced increase in Cldn-7 and -12 expression.
Absorption/drug effects ; Caco-2 Cells ; Calcium/metabolism ; Claudins/genetics/*metabolism ; Dose-Response Relationship, Drug ; Gene Expression/drug effects ; Humans ; Hydrogen-Ion Concentration ; Magnesium/*metabolism ; Omeprazole/*pharmacology ; Proton Pump Inhibitors/*pharmacology ; Receptors, Calcium-Sensing/metabolism

OBJECTIVETo observe the clinical effect and mechanism of migraine treated with pine needle moxibustion.

METHODSForty-three patients were randomly divided into 2 groups of pine needle moxibustion group (group A, 21 cases) and medicated thread moxibustion of Zhuang medicine group (group B, 22 cases). Same acu-points were selected as the main points for both groups, namely Fengchi (GB 20), Baihui (GV 20), Taiyang (EX-HN 5), Shuaigu (GB 8), Cuanzhu (BL 2), Sizhukong (TE 23), Yanglingquan (GB 34), Waiguan (TE 5) and Ashi points. Pine needle moxibustion was applied for the group A. Processed lighted pine needles were banded together with one even head to do moxibustion on acupoints or pain points. While, lighted medicated thread was adopted for the group B to do moxibustion. Therapeutic effects, the content of high-sensitivity C-reactive protein (hs-CRP), Mg2+ in the serum and the degree of pain of the two groups were compared.

RESULTS(1) In the group A, the complete remission rate was 47.6% (10/21) and the effective rate was 90.5% (19/21). In the group B, the complete remission rate was 13.6% (3/22) and the effective rate was 50.0% (11/22). The two rates in the group A were superior to those in the group B (both P < 0.01); (2) In the group A, the content of hs-CRP was decreased from (4.29 +/- 0.98) mg/L to (2.11 +/- 0.87) mg/L, and Mg2+ was increased from (0.67 +/- 0.28) mmol/L to (1.07 +/- 0.16) mmol/L. In the group B, the contents of the above mentioned indices were respectively decreased from (4.30 +/- 1.07) mg/L to (3.38 +/- 1.15) mg/L and increased from (0.68 +/- 0.21) mmol/L to (0.88 +/- 0.25) mmol/L. There were significant differences between the two groups after treatment (both P < 0.05). (3) The degree of pain in the group A after treatment was much lower than that in the group B (P < 0.05).

CONCLUSIONThe clinical effect of migraine treated with pine needle moxibustion is better than that with the medicated thread moxibustion of Zhuang medicine. And it has obvious regulation effect on the levels of hs-CRP and Mg2+ in the serum of patients.

Acupuncture Points ; Adolescent ; Adult ; C-Reactive Protein ; metabolism ; Female ; Humans ; Magnesium ; blood ; Male ; Middle Aged ; Migraine Disorders ; metabolism ; therapy ; Moxibustion ; Young Adult