Methylglyoxal activates transient receptor potential A1/V1 via reactive oxygen species in the spinal dorsal horn.

Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the effect of MGO on spontaneous excitatory postsynaptic currents (sEPSC) in rat spinal dorsal horn neurons using blind whole-cell patch-clamp recording. Perfusion of MGO increased the frequency and amplitude of sEPSC in spinal horn neurons in a concentration-dependent manner. Additionally, MGO administration increased the number of miniature EPSC (mEPSC) in the presence of tetrodotoxin, a sodium channel blocker. However, 6-cyano-7-nitroqiunocaline-2,3-dione (CNQX), an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSC by MGO. HC-030031, a TRP ankyrin-1 (TRPA1) antagonist, and capsazepine, a TRP vanilloid-1 (TRPV1) antagonist, inhibited the action of MGO. Notably, the effects of MGO were completely inhibited by HC-030031 and capsazepine. MGO generates reactive oxygen species (ROS) via AGEs. ROS also potentially induce pain via TRPA1 and TRPV1 in the spinal dorsal horn. Furthermore, we examined the effect of MGO in the presence of N-tert-butyl-α-phenylnitrone (PBN), a non-selective ROS scavenger, and found that the effect of MGO was completely inhibited. These results suggest that MGO increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons through TRPA1, TRPV1, and ROS and could enhance excitatory synaptic transmission.

Effect of magnesium oxide nanoparticles and LED irradiation on the viability and differentiation of human stem cells of the apical papilla.

PURPOSE: Currently, regenerative endodontic treatments are gaining more and more attention, and stem cells play a significant role in these treatments. In order to enhance stem cell proliferation and differentiation, a variety of methods and materials have been used. The purpose of this study was to determine the effects of magnesium oxide nanoparticles and LED irradiation on the survival and differentiation of human stem cells from apical papilla. METHODS: The MTT test was used to measure the cell survival of SCAPs that had been exposed to different concentrations of magnesium oxide nanoparticles after 24 and 48 h, and the concentration with the highest cell survival rate was picked for further studies. The cells were classified into four distinct groups based on their treatment: (1) control, which received no exposure, (2) exposure to magnesium oxide nanoparticles, (3) exposure to light emitting diode (LED) irradiation (635 nm, 200 mW/cm2) for 30 s, (4) exposure simultaneously with magnesium oxide nanoparticles and LED irradiation. A green approach was employed to synthesize magnesium oxide nanoparticles. Quantitative real time PCR was used to measure the gene expression of osteo/odontogenic markers such as BSP, DSPP, ALP and DMP1 in all four groups after treatment, and Alizarin red S staining (ARS) was used to determine the osteogenic differentiation of SCAPs by demonstrating the Matrix mineralization. RESULTS: The highest viability of SCAPs was observed after 24 h in concentration 1 and 10 µg/mL and after 48 h in concentration 1 µg/mL, which were not significantly different from the control group. In both times, the survival of SCAPs decreased with increasing concentration of magnesium oxide nanoparticles (MgONPs). According to the results of Real-time PCR, after 24 and 48 h, the highest differentiation of BSP, DMP1, ALP and DSPP genes was observed in the LED + MgONPs group, followed by MgONPs and then LED, and in all 3 experimental groups, it was significantly higher than control group (P < 0.05). Also, after 24 and 48 h, the density of ARS increased in all groups compared to the control group, and the highest density was observed in the MgONPs + LED and MgONPs groups. CONCLUSION: This research concluded that exposure to SCAPs, MgONPs, and LED irradiation has a significant effect on enhancing gene expression of odontogenic/osteogenic markers and increasing matrix mineralization.

Synergistic effect of green synthesis magnesium oxide nanoparticles and seaweed extract on improving water quality, health benefits, and disease resistance in Nile tilapia.

This study aimed to evaluate the effect of adding liquid extract of algae (Hypnea musciformis, Grateloupia acuminata, and Sargassum muticum) (HGS) and Magnesium oxide nanoparticles (MgO NPs) using this extract to rear water of Oreochromis niloticus, on improving culture water indices, growth performance, digestive enzyme, hemato-biochemical characters, immune, antioxidative responses, and resistance after challenged by Aeromonas hydrophila with specific refer to the potential role of the mixture in vitro as resistance against three strains bacteria (Aeromonas sobria, Pseudomonas fluorescens, P. aeruginosa) and one parasite (Cichlidogyrus tilapia). The first group represented control, HGS0, whereas the other group, HGS5, HGS10, and HGS15 mL-1 of liquid extract, as well as all groups with 7.5 µg mL-1 MgO-NPs added to culture water of O. niloticus, for 60 days. Data showed that increasing levels at HGS 10 and HGS15 mL-1 in to-culture water significantly enhanced growth-stimulating digestive enzyme activity and a significantly improved survival rate of O. niloticus after being challenged with A. hydrophila than in the control group. The total viability, coliform, fecal coliform count, and heavy metal in muscle partially decreased at HGS 10 and HGS15 mL-1 than in the control group. Correspondingly, the highest positive effect on hemato-biochemical indices was noticed at levels HGS 10 and HGS15 mL-1. Fish noticed an improvement in immune and antioxidant indices compared to control groups partially at HGS 10 and HGS15 mL-1. Interestingly, fish cultured in rearing water with the mixture provided downregulated the related inflammatory genes (HSP70, TNF, IL-1ß, and IL-8) partially at HGS15 mL-1. In vitro, the mixture showed positive efficiency as an antibacterial and partially antiparasitic at HGS 10 and HGS15 mL-1. This study proposes utilizing a mixture of (HGS) and (MgO-NPs) with optimum levels of 10-15 mL-1 in cultured water to improve water indices, growth, health status, and increased resistance of O. niloticus against bacterial and parasitic infection.

Complement terminal pathway inhibition reduces peritoneal injuries in a rat peritonitis model.

Peritonitis and the resulting peritoneal injuries are common problems that prevent long-term peritoneal dialysis (PD) therapy in patients with end-stage kidney diseases. Previously, we have analyzed the relationship between the complement system and progression of peritoneal injuries associated with PD, particularly focusing on the early activation pathways and effects of the anaphylatoxins. We here utilized a novel mAb 2H2 that blocks assembly of the membrane attack complex (MAC) to investigate roles of the complement terminal pathway in PD-associated peritoneal injury. We intraperitoneally injected mAb 2H2 anti-C5b-7 (2.5 or 5 mg/rat) once or twice over the five-day course of the experiment to investigate the effects of inhibiting formation of MAC in a fungal rat peritonitis model caused by repeated intraperitoneal administration of zymosan after methylglyoxal pretreatment (Zy/MGO model). Rats were sacrificed on day 5 and macroscopic changes in both parietal and visceral peritoneum evaluated. Peritoneal thickness, the abundance of fibrinogen and complement C3 and MAC deposition in tissue and accumulation of inflammatory cells were pathologically assessed. The results showed that mAb 2H2, but not isotype control mAb, reduced peritoneal thickness and accumulation of inflammatory cells in a dose and frequency-dependent manner in the Zy/MGO model. These effects were accompanied by decreased C3, MAC, and fibrinogen deposition in peritoneum. In conclusion, in the rat Zy/MGO model, complement terminal pathway activation and MAC formation substantially contributed to development of peritoneal injuries, suggesting that MAC-targeted therapies might be effective in preventing development of peritoneal injuries in humans.

Effects of magnesium oxide and copper oxide nanoparticles on biofilm formation ofEscherichia coliandListeria monocytogenes.

Biofilms formed in food-processing environments are of special importance as they have the potential to act as a persistent source of microbial contamination that may lead to food spoilage or transmission of diseases. The creation of microbial biofilms, which can be a source of food product contamination with food spoilage and foodborne pathogenic bacteria, is one of the most critical elements in the food industry. The goal of this study was to see how well magnesium oxide (MgO) and copper oxide (CuO) nanoparticles (NPs) inhibited growth and biofilm formation of two common foodborne bacterial pathogens. This study was completed in the year 2020. Resazurin reduction and micro-dilution procedures were used to assess the minimum inhibitory concentration (MIC) of magnesium oxide and copper oxide nanoparticles forEscherichia coliO157: H7 (ATCC 35 218) andListeria monocytogenes(L. monocytogenes) (ATCC 19 118). The bacterial adhesion to hydrocarbon technique was used to determine the cell-surface hydrophobicity of the selected bacteria. The surface assay was also used to calculate the influence of the NPs coated surfaces on the biofilm formation of the selected bacteria. Magnesium oxide nanoparticles had MICs of 2 and 2 mg ml-1, while copper oxide nanoparticles had MICs of 0.16 and 1 mg ml-1againstE. coliandL. monocytogenes, respectively. At the MIC, the magnesium and copper nanoparticles inhibited biofilm formation ofE. coliandL. monocytogenesby 89.9 and 96.6 percent and 93.6 and 98.7 percent, respectively. The hydrophobicity ofE. coliandL. monocytogeneswas determined to be 74% and 67%, respectively. The surface assay revealed a substantial reduction in bacterial adhesion and colonization on NPs-coated surfaces. Both compounds had inhibitory effects onE. coliandL. monocytogenes, according to our findings. Even at sub-MICs, NPs were found to be able to prevent biofilm development. The microbial count and production of microbial biofilms were reduced on surfaces coated with MgO and CuO nanoparticles. MgO and CuO nanoparticles can be utilized as a cleaning agent for surfaces to avoid the formation of foodborne bacterial biofilms, which is important for public health.

Silk sericin conjugated magnesium oxide nanoparticles for its antioxidant, anti-aging, and anti-biofilm activities.

The Silk sericin protein was conjugated with magnesium oxide (MgO) nanoparticles to form SS-MgO-NPs . UV, XRD, FTIR, SEM, DLS, and EDX were used to confirm the formation of SS-MgO-NPs. The absorption band of SS-MgO-NPs using UV-visible spectra was observed at 310 nm, with an average size of the nanoparticles was 65-88 nm analyzed from DLS. The presence of alcohol, CN, and CC, alkanes, alkenes, and cis alkenes, in silk sericin, is confirmed by FT-IR and may act as a stabilizing agent. Later SS-MgO-NPs were evaluated for antioxidant, antibacterial, anti-biofilm, ,anti-aging, and anticancer properties. The SS-MgO-NPs inhibited the formation of biofilm of Pseudomonas aeruginosa and Bacillus cereus. The blood compatibility of SS-MgO-NPs, delaying coagulation was observed using human, blood, and goat blood samples. The SS-MgO-NPs exhibited significant anticancer activity on MCF-7 (IC50 207.6 µg/mL) cancer cell lines. Correspondingly, SS-MgO-NPs demonstrated dose-dependent inhibition of the enzymes in the following order collagenase > elastase > tyrosinase > hyaluronidase, with IC50 values of 75.3, 85.3, 133.6, and 156.3 µgmL-1, respectively. This exhibits the compoundposses anti-aging properties. So, in in vitro settings, SS-MgO-NPs can be used as an antibacterial, anti-aging, and anticancer agent. Additionally, in vivo research is necessary to validate its therapeutic applications.

Magnesium oxide nanoparticles improved vegetative growth and enhanced productivity, biochemical potency and storage stability of harvested mustard seeds.

A field study was conducted to investigate the influence of MgO-NPs priming on growth and development of mustard. Priming of mustard seeds before sowing with MgO-NPs at concentration 10, 50, 100, and 150 µg/ml enhanced the vegetative parameters of plants, with considerable increase in leaf area. MgO-NPs exposure increased the photosynthetic pigment accumulation in mustard that led to increase in biomass, carbohydrate content, and the yield in terms of total grain yield. Increased chlorophyll has simultaneously increased the oxidative stress in plants, and hence stimulated their antioxidant potential. A consistent increase was observed in the content of mustard polyphenols and activity of SOD, CAT, and APX on MgO-NPs exposure. MgO-NPs induced oxidative stress further reduced the protein content and bioavailability in mustard. We further, evaluated the influence of MgO-NPs on the quality of mustard harvested seeds. The seeds harvested from nanoprimed mustard possessed increased antioxidant potential and reduced oxidative stress. The carbohydrate and protein accumulation was significantly enhanced in response to nanopriming. Reduced chlorophyll content in seeds obtained from nanoprimed mustard indicated their potential for disease resistance and stability on long term storage. Therefore, the seeds harvested from MgO-NPs primed mustard were biochemically rich and more stable. Therefore, MgO-NPs priming can be potentially used as a novel strategy for growth promotion in plants where leaves are economically important and a strategy to enhance the seed quality under long term storage conditions.

Angiotensin II reduces glyoxalase 1 activity and expression in vascular smooth muscle cells: Implications for diabetic vascular complications.

Angiotensin II (Ang II), a key mediator of vascular diseases, is linked to methylglyoxal (MGO) formation, a by-product of glucose metabolism implicated in vascular complications. The glyoxalase system, consisting of glyoxalase 1 (Glo1) and reduced glutathione (GSH), is responsible for detoxifying MGO. This study investigated the effect of Ang II on Glo1 activity and expression in vascular smooth muscle cells (VSMCs). Primary VSMCs were isolated from rat aortas and exposed to Ang II under standard or high glucose conditions. We examined Glo1 activity, expression, intracellular GSH, and methylglyoxal-derived hydroimidazolone 1 (MG-H1) levels. We also analyzed the expressions of nuclear factor-κB (NF-κB) p65 and nuclear factor erythroid 2-related factor 2 (Nrf2) as potential regulators of Glo1 expression. The results demonstrated that Ang II reduced Glo1 activity, expression, and GSH levels while increasing MG-H1 levels in VSMCs. Telmisartan and irbesartan, AT1R blockers, restored Glo1 activity, expression, and GSH levels and alleviated MG-H1 levels. Treatment with AT1R blockers or inhibitors targeting signaling pathways involved in Ang II-induced responses mitigated these effects. High glucose exacerbated the reduction in Glo1 activity and expression. In conclusion, this study provides evidence that Ang II reduces Glo1 activity and expression in VSMCs, which may contribute to developing vascular complications in diabetes. AT1R blockers and inhibitors targeting specific signaling pathways show potential in restoring Glo1 function and mitigating MGO-associated damage. These findings highlight the complex interactions between RAS, MGO, and vascular diseases, highlighting potential therapeutic targets for diabetic vascular complications.

Umbelliferone protects against methylglyoxal-induced HUVECs dysfunction through suppression of apoptosis and oxidative stress.

Methylglyoxal (MGO), a cytotoxic metabolite of glycolysis, can cause endothelial cells impairment, which is tightly associated with diabetic vascular complication. Umbelliferone, a derivative of coumarin, participates in various pharmacological activities. This study aimed to determine the effectiveness of umbelliferone in MGO-induced apoptosis and oxidative stress in endothelial cells. In this study, it has been indicated that umbelliferone inhibited MGO-induced human umbilical vein endothelial cells (HUVECs) cytotoxicity, apoptosis, Bax/Bcl-2 protein ratio, the activity of cleaved-caspase-3, and mitochondrial membrane potential loss. Furthermore, we found that umbelliferone inhibited MGO-induced activation of mitogen-activated protein kinases and nuclear factor-κB signaling pathways in HUVECs. In addition, umbelliferone could suppress oxidative stress, as evidenced by decrease of reactive oxygen species and malondialdehyde (MDA) generation, and increase of superoxide dismutase and glutathione peroxidase contents. Moreover, we found that umbelliferone can activate Nrf2/HO-1 signaling. Importantly, silencing of Nrf2 signaling clearly eliminated the anti-oxidative stress of umbelliferone, whereas umbelliferone pretreatment had no effect on Nrf2 overexpressing HUVECs. Altogether, this study suggested that umbelliferone pretreatment has a protective effect on MGO-induced endothelial cell dysfunction through inhibiting apoptosis and oxidative stress.

Effects on rumen pH and feed intake of a dietary concentrate challenge in cows fed rations containing pH modulators with different neutralizing capacity.

Forty-five Holstein lactating cows (41 ± 8.8 kg/d of milk yield, 96 ± 35.6 days in milk, and 607 ± 80.4 kg of body weight) were enrolled in this study to assess the effects of diets supplemented with sodium bicarbonate or a magnesium-based product and their corresponding differences in dietary cation-anion difference (DCAD) on rumen pH, rumen microbial population, and milk performance of dairy cattle exposed to an induced decrease in rumen pH through a dietary challenge. Cows were randomly allocated to 3 total mixed rations (TMR) differing in the type of supplement to modulate rumen pH: (1) control, no supplementation; (2) SB, supplemented with 0.82% of sodium bicarbonate with a neutralizing capacity (NC) of 12 mEq/g; and (3) MG, supplemented with 0.25% of magnesium oxide (pHix-Up, Timab Magnesium) with a NC of 39 mEq/g. Thus, SB and MG rations had, in theory, the same NC. The 3 TMR differed for control, SB, and MG in their DCAD-S (calculated considering Na, K, Cl, and S), which was on average 13.2, 21.2, and 13.7 mEq/100 g, respectively, or DCAD-Mg (calculated accounting for Mg, Ca, and P), which was 31.4, 41.2, and 35.2 mEq/100 g, respectively. The study lasted 63 d, with the first 7 d serving as a baseline, followed by a fortnightly progressive decrease of dietary forage-to-concentrate ratio (FCR) starting at 48:52, then 44:56, then 40:60, and finishing at 36:64. Individual dry matter intake (DMI) was recorded daily. Seven cows per treatment were equipped with electronic rumen boluses to monitor rumen pH. Control and SB cows consumed less dry matter (DM; 23.5 ± 0.31 kg/d) than MG cows (25.1 ± 0.31 kg/d) when fed dietary FCR of 44:56 and 40:60. Energy-corrected milk decreased from 40.8 ± 1.21 to 39.5 ± 1.21 kg/d as dietary FCR decreased, independently of dietary treatments. Rumen pH decreased and the proportion of the day with rumen pH <5.8 increased as dietary FCR decreased, and at low dietary FCR (i.e., 36:64) rumen pH was greater in MG cows than in control and SB cows. Reducing the DCAD-S from 28 to 18 mEq/100 g or the DCAD-Mg from 45 to 39 mEq/kg had no effects on DMI or milk yield. Cows supplemented with ∼62 g/d of magnesium oxide (pHix-Up) maintained a greater rumen pH and consumed more DM than cows supplemented with ∼200 g/d of sodium bicarbonate when fed a diet with low FCR.

Production, physiological response, and calcium and magnesium balance of lactating Holstein cows fed different sources of supplemental magnesium with or without ruminal buffer.

The objective of this study was to evaluate the effects of dietary replacement of magnesium oxide (MgO) with calcium-magnesium hydroxide [CaMg(OH)2] and its interaction with ruminal buffer (sodium sesquicarbonate) supplementation on production, Ca and Mg balance, and overall physiological response of mid-lactation Holstein dairy cows. Sixty cows averaging 40.5 ± 7.0 kg of milk/d were used. Treatments were assigned following a 2 × 2 factorial arrangement: (1) MgO, (2) MgO + buffer, (3) CaMg(OH)2, or (4) CaMg(OH)2 + buffer. Diets were formulated to have 16.5% of crude protein, 1.82 Mcal/kg of net energy for lactation, 0.67% Ca, 0.39% P, and 0.25% Mg, all on a dry matter (DM) basis. Treatments were individually top dressed. Milk production, composition, and DM intake were evaluated. A subsample of 20 cows were randomly selected for the evaluation of Ca and Mg balance, blood gases, and electrolytes. Ruminal fluid was also collected for evaluation of pH and Ca and Mg solubility. Effects of Mg source, buffer, and the interaction Mg source × buffer were analyzed through orthogonal contrasts. An interaction of Mg source × buffer was found for DM intake and feed efficiency, in which cows fed CaMg(OH)2 had a similar feed efficiency regardless of ruminal buffer inclusion; however, when cows were fed MgO, the inclusion of buffer reduced feed efficiency. No effects on body weight and milk yield were observed. Buffer addition tended to increase the concentrations of fat, protein, and solids-not-fat, without affecting the yields of these milk components. Magnesium source and buffer did not affect ruminal fluid, blood, urine, or fecal pH; however, buffer supplementation increased urinary pH. Treatment with CaMg(OH)2 increased blood concentration of HCO3-, total CO2, and base excess compared with cows fed MgO. No differences were observed in the ruminal solubility of Ca and Mg or on milk or urinary Ca and Mg excretion. Greater plasma Mg concentration was observed for animals fed MgO compared with cows fed CaMg(OH)2; however, both sources were above the threshold recommended in the literature for dairy cows. Also, a reduction in fecal Mg excretion was observed in animals fed CaMg(OH)2. In summary, we provide evidence that CaMg(OH)2 could replace MgO without affecting performance, overall physiological response, or Ca and Mg balance of mid-lactating dairy Holstein cows.

Mechanisms underlying the methylglyoxal-induced enhancement of uridine diphosphate-mediated contraction in rat femoral artery.

Although femoral artery dysfunctions, including aberrant vascular reactivity to vasoactive substances, are common in many chronic disorders, such as diabetes and hypertension, their inducible and/or progressive factors remain unclear. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of various chronic disorders. However, its direct correlation with extracellular nucleotides including uridine 5'-diphosphate (UDP) in the femoral artery function is currently unknown. Therefore, we investigated the acute effect of MGO on UDP-induced contraction in the rat femoral artery. MGO (4.2 × 10-4 M for 1 h) enhanced the UDP-induced contraction. This enhancement was not abolished in all conditions, including nitric oxide synthase inhibition, cyclooxygenase inhibition, or endothelial denudation. In the endothelium-denuded arteries, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (10-5 M) suppressed the UDP-induced contraction in both control and MGO-treated groups, while MGO enhanced the p38 MAPK activation regardless of the UDP presence. Moreover, in the endothelium-denuded arteries, the Syk tyrosine kinase inhibitor piceatannol (10-5 M) suppressed the UDP-induced contraction. These results suggest that MGO augments UDP-induced contraction in rat femoral arteries and that this may be partly due to the alterations in the activities of Syk tyrosine kinase and p38 MAPK in the smooth muscle.

Effects of temperature, pH and sodium chloride on antimicrobial activity of magnesium oxide nanoparticles against E. coli O157:H7.

AIM: This study was done to determine the effects of temperature, pH and sodium chloride (NaCl) on antimicrobial activity of magnesium oxide (MgO) nanoparticles (NPs) against E. coli O157:H7. METHODS AND RESULTS: Culture conditions were established by varying the pH (5.0, 7.2 and 9.0), NaCl concentration (0.5, 2.0, 3.5 and 5.0%, w/v), and incubation temperatures (4, 12, 22 and 37°C). At each condition, the antimicrobial activities of MgO-NPs (0, 1, 2 and 4 mg/ml) against E. coli O157:H7 were measured. Four-way analysis of variance indicated interactions among all factors had a significant effect (p ≤ 0.05) on the antimicrobial activity of MgO-NPs. The concentration of MgO-NPs necessary to cause a 5-log reduction of E. coli O157:H7 under the most inhibitory conditions (37°C, pH 9.0, and 5.0% NaCl) was 0.50 mg/ml of MgO-NPs. CONCLUSION: The antimicrobial activity of the MgO-NPs increased significantly (p ≤ 0.05) with increased temperature, pH and NaCl concentration in TSB. SIGNIFICANCE AND IMPACT OF THE STUDY: The influence of intrinsic and extrinsic factors on antimicrobial activity of MgO-NPs we found will contribute to the development of microbial decontamination strategies using MgO in the food industry.

Effects of replacing magnesium oxide with calcium-magnesium carbonate with or without sodium bicarbonate on ruminal fermentation and nutrient flow in vitro.

The objective of this study was to evaluate the effects of replacing magnesium oxide (MgO) with calcium-magnesium carbonate [CaMg(CO3)2] on ruminal fermentation with or without the addition of sodium bicarbonate (NaHCO3). Eight fermentors of a dual-flow continuous-culture system were distributed in a replicated (2) 4 × 4 Latin square design in a 2 × 2 factorial arrangement of treatments (magnesium sources × NaHCO3). The treatments tested were 0.21% MgO [MgO; dry matter (DM) basis; 144.8 mEq of dietary cation-anion difference (DCAD)]; 0.21% MgO + 0.50% NaHCO3 (MgO+NaHCO3; DM basis; 205.6 mEq of DCAD); 1.00% CaMg(CO3)2 [CaMg(CO3)2; DM basis; 144.8 mEq of DCAD]; and 1.00% CaMg(CO3)2 + 0.50% NaHCO3 [CaMg(CO3)2+NaHCO3; DM basis; 205.6 mEq of DCAD]. Diets were formulated to have a total of 0.28% of Mg (DM basis). The experiment consisted of 40 d, which was divided into 4 periods of 10 d each, where 7 d were used for adaptation and 3 d for sampling to determine pH, volatile fatty acids (VFA), ammonia (NH3-N), lactate, mineral solubility, N metabolism, and nutrient digestibility. The effects of Mg source [MgO vs. CaMg(CO3)2], NaHCO3 (with vs. without), and the interaction were tested with the MIXED procedure of SAS version 9.4 (SAS Institute). There was no Mg source × NaHCO3 interaction in the pH variables and mineral solubility, and Mg sources evaluated did not affect the variables related to ruminal pH and solubility of Mg. On the other hand, the inclusion of NaHCO3 increased the pH daily average, independent of Mg source, which led to a reduced time that pH was below 5.8 and decreased area under the curve. Total VFA and lactate concentration were similar among treatments regardless of NaHCO3 and Mg source; however, the molar proportion of isobutyrate and NH3-N concentration were lower in diets with CaMg(CO3)2 compared with MgO. Moreover, NaHCO3 inclusion increased NH3-N, total daily NH3-N flow, isobutyrate concentration, and acid detergent fiber digestibility. Our results showed that CaMg(CO3)2 leads to a lower NH3-N concentration and isobutyrate proportion. Therefore, because most of the tested variables were not significantly different between MgO and CaMg(CO3)2 when combined or not with NaHCO3, CaMg(CO3)2 can be a viable alternative source to replace MgO in dairy cow diets without affecting mineral solubility, ruminal pH, nutrient digestibility, total VFA, and the main ruminal VFA. Although Mg sources are known to have an alkalizing effect, NaHCO3 inclusion in diets with Mg supplementation allowed an increase in ruminal pH, as well as an increase in isobutyrate and NH3-N flow.

Glycation of Tie-2 Inhibits Angiopoietin-1 Signaling Activation and Angiopoietin-1-Induced Angiogenesis.

The impairment of the angiopoietin-1 (Ang-1)/Tie-2 signaling pathway has been thought to play a critical role in diabetic complications. However, the underlying mechanisms remain unclear. The present study aims to investigate the effects of Tie-2 glycation on Ang-1 signaling activation and Ang-1-induced angiogenesis. We identified that Tie-2 was modified by advanced glycation end products (AGEs) in aortae derived from high fat diet (HFD)-fed mice and in methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). MGO-induced Tie-2 glycation significantly inhibited Ang-1-evoked Tie-2 and Akt phosphorylation and Ang-1-regulated endothelial cell migration and tube formation, whereas the blockade of AGE formation by aminoguanidine remarkably rescued Ang-1 signaling activation and Ang-1-induced angiogenesis in vitro. Furthermore, MGO treatment markedly increased AGE cross-linking of Tie-2 in cultured aortae ex vivo and MGO-induced Tie-2 glycation also significantly decreased Ang-1-induced vessel outgrow from aortic rings. Collectively, these data suggest that Tie-2 may be modified by AGEs in diabetes mellitus and that Tie-2 glycation inhibits Ang-1 signaling activation and Ang-1-induced angiogenesis. This may provide a novel mechanism for Ang-1/Tie-2 signal dysfunction and angiogenesis failure in diabetic ischaemic diseases.

Study on Enhancing the Corrosion Resistance and Photo-Thermal Antibacterial Properties of the Micro-Arc Oxidation Coating Fabricated on Medical Magnesium Alloy.

Photo-thermal antibacterial properties have attracted much attention in the biomedical field because of their higher antibacterial efficiency. Through fabricating micro-arc oxidation coatings with different treating current densities set on a Mg-Zn-Ca alloy, the present study tried to systematically investigate and optimize the corrosion resistance and photo-thermal antibacterial properties of MAO coatings. The results indicated that different current densities had great influence on the corrosion resistance and photo-thermal property of the MAO coatings, and a current density at 30 A·dm-2 exhibited the best corrosion resistance, light absorption capacity at 808 nm, and photo-thermal capability, simultaneously with good antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This photo-thermal property of MAO coatings was probably related to the effect of current density on MgO content in the coating that could promote the separation of photo-generated electron carriers and hinder the recombination of photo-generated electron carriers and holes.

Dental Composites with Magnesium Doped Zinc Oxide Nanoparticles Prevent Secondary Caries in the Alloxan-Induced Diabetic Model.

Antibacterial restorative materials against caries-causing bacteria are highly preferred among high-risk patients, such as the elderly, and patients with metabolic diseases such as diabetes. This study aimed to enhance the antibacterial potential of resin composite with Magnesium-doped Zinc oxide (Mg-doped ZnO) nanoparticles (NPs) and to look for their effectiveness in the alloxan-induced diabetic model. Hexagonal Mg-doped ZnO NPs (22.3 nm diameter) were synthesized by co-precipitation method and characterized through ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) analysis. The Mg-doped ZnO NPs (1, 2.5 and 5% w/w) were then evaluated for antibacterial activity using a closed system in vitro biofilm model. Significant enhancement in the antibacterial properties was observed in composites with 1% Mg-doped ZnO compared to composites with bare ZnO reinforced NPs (Streptococcus mutans, p = 0.0005; Enterococcus faecalis, p = 0.0074, Saliva microcosm, p < 0.0001; Diabetic Saliva microcosm, p < 0.0001). At 1−2.5% Mg-doped ZnO NPs concentration, compressive strength and biocompatibility of composites were not affected. The pH buffering effect was also achieved at these concentrations, hence not allowing optimal conditions for the anaerobic bacteria to grow. Furthermore, composites with Mg-doped ZnO prevented secondary caries formation in the secondary caries model of alloxan-induced diabetes. Therefore, Mg-doped ZnO NPs are highly recommended as an antibacterial agent for resin composites to avoid biofilm and subsequent secondary caries formation in high-risk patients.

Effect of Biofunctional Green Synthesized MgO-Nanoparticles on Oxidative-Stress-Induced Tissue Damage and Thrombosis.

The present study describes the green biofunctional synthesis of magnesium oxide (MgO) nanoparticles using the aqueous Tarenna asiatica fruit extract. The characterization of Tarenna asiatica fruit extract MgO nanoparticles (TAFEMgO NPs) was achieved by X-ray powder diffraction, UV-Vis spectroscopy, FTIR, TEM, SEM, and energy-dispersive X-ray diffraction. TAFEMgO NPs scavenged the DPPH free radicals with an IC50 value of 55.95 µg/µL, and it was highly significant compared to the standard. To authenticate the observed antioxidant potential of TAFEMgO NPs, oxidative stress was induced in red blood cells (RBC) using sodium nitrite (NaNO2). Interestingly, TAFEMgO NPs ameliorated the RBC damage from oxidative stress by significantly restoring the stress parameters, such as the protein carbonyl content (PCC), lipid peroxidation (LPO), total thiol (TT), super-oxide dismutase (SOD), and catalase (CAT). Furthermore, oxidative stress was induced in-vivo in Sprague Dawley female rats using diclofenac (DFC). TAFEMgO NPs normalized the stress parameters in-vivo and minimized the oxidative damage in tissues. Most importantly, TAFEMgO NPs restored the function and architecture of the damaged livers, kidneys, and small intestines by regulating biochemical parameters. TAFEMgO NPs exhibited an anticoagulant effect by increasing the clotting time from 193 s in the control to 885 s in the platelet rich plasma. TAFEMgO NPs prolonged the formation of the clot process in the activated partial thromboplastin time and the prothrombin time, suggest the effective involvement in both intrinsic and extrinsic clotting pathways of the blood coagulation cascade. TAFEMgO NPs inhibited adenosine di-phosphate (ADP)-induced platelet aggregation. TAFEMgO NPs did not show hemolytic, hemorrhagic, and edema-inducing properties at the tested concentration of 100 mg/kgbody weight, suggesting its non-toxic property. In conclusion, TAFEMgO NPs mitigates the sodium nitrite (NaNO2)- and diclofenac (DFC)-induced stress due to oxidative damage in both in vitro and in vivo experimental models.

Polysaccharides as Green Fuels for the Synthesis of MgO: Characterization and Evaluation of Antimicrobial Activities.

The synthesis of structured MgO is reported using feedstock starch (route I), citrus pectin (route II), and Aloe vera (route III) leaf, which are suitable for use as green fuels due to their abundance, low cost, and non-toxicity. The oxides formed showed high porosity and were evaluated as antimicrobial agents. The samples were characterized by energy-dispersive X-ray fluorescence (EDXRF), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The crystalline periclase monophase of the MgO was identified for all samples. The SEM analyses show that the sample morphology depends on the organic fuel used during the synthesis. The antibacterial activity of the MgO-St (starch), MgO-CP (citrus pectin), and MgO-Av (Aloe vera) oxides was evaluated against pathogens Staphylococcus aureus (ATCC 6538P) and Escherichia coli (ATCC 8739). Antifungal activity was also studied against Candida albicans (ATCC 64548). The studies were carried out using the qualitative agar disk diffusion method and quantitative minimum inhibitory concentration (MIC) tests. The MIC of each sample showed the same inhibitory concentration of 400 µg. mL-1 for the studied microorganisms. The formation of inhibition zones and the MIC values in the antimicrobial analysis indicate the effective antimicrobial activity of the samples against the test microorganisms.

Magnesium and Zinc Oxide Nanoparticles from Datura alba Improve Cognitive Impairment and Blood Brain Barrier Leakage.

Epilepsy is a neurological disorder involving persistent spontaneous seizures and uncontrolled neuronal excitability that leads to cognitive impairments and blood-brain barrier (BBB) disruption. Currently available antiepileptic drugs present side effects and researchers are trying to discover new agents with properties to overcome these drawbacks. The aim was to synthesize magnesium oxide (MgO) and zinc oxide (ZnO) nanoparticles from Datura alba fresh leaf extracts and evaluate their anti-epileptic potential in mice kindling or a repetitive seizures model. The phytoassisted synthesized nanoparticles were characterized using spectroscopy; FT-IR, XRD, SEM, and EDX. Analysis of the NPs confirmed the crystalline pleomorphic shape using the salts of both zinc and magnesium possibly stabilized, functionalized and reduced by bioactive molecules present in plant extract. By using several characterization techniques, NPs were confirmed. UV-Vis spectroscopy of biologically produced ZnO and MgO revealed distinctive peaks at 380 nm and 242 nm, respectively. Our findings categorically demonstrated the reductive role of biomolecules in the formation of ZnO and MgO NPs. The mice kindling model was induced using seven injections of Pentylenetetrazole (PTZ, 40 mg/kg, i.p) for 15 days alternatively. The results showed that mice post-treated with either ZnO or MgO nanoparticles (10 mg/kg, i.p) significantly improved in respect of behavior and memory as confirmed in the Morris water maze (MWM), open field (OF), novel object recognition (NOR) test compared with PTZ treated mice. Furthermore, the ZnO and MgO nanoparticle treatment also maintained the integrity of the BBB, reducing the leakage, as confirmed by Evans blue dye (EBD) compared with PTZ treated mice only. In summary, the current finding demonstrates that green synthesized ZnO and MgO nanoparticles have neuroprotective, ant-epileptic potential, molecular mechanisms, and clinical implications need to be further explored.