PMID: 

Biol Trace Elem Res. 2019 Nov 5. Epub 2019 Nov 5. PMID: 31691193

Abstract Title: 

The Role of Magnesium in Pathophysiology and Migraine Treatment.

Abstract: 

Migraine is one of the most common recurrent types of headache and is the seventh cause of disability. This neurological disorder is characterized by having pain in head and other various symptoms such as nausea, emesis, photophobia, phonophobia, and sometimes visual sensory disorders. Magnesium (Mg) is a necessary ion for human body and has a crucial role in health and life maintenance. One of the main roles of Mg is to conserve neurons electric potential. Therefore, magnesium deficiency can cause neurological complications. Migraine is usually related to low amounts of Mg in serum and cerebrospinal fluid (CSF). Deficits in magnesium have significant role in the pathogenesis of migraine. Mg has been extensively used in migraine prophylaxis and treatment. This review summarizes the role of Mg in migraine pathogenesis and the potential utilizations of Mg in the prevention and treatment of migraine with the emphasis on transdermal magnesium delivery.

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PMID: 

Environ Res. 2020 Jan ;180:108890. Epub 2019 Nov 5. PMID: 31718786

Abstract Title: 

Exposure to airborne fine particulate matter is associated with impaired endothelial function and biomarkers of oxidative stress and inflammation.

Abstract: 

Epidemiological evidence suggests that exposure to air pollution is a leading risk factor for cardiovascular disease (CVD). However, there is little direct evidence linking exposure to vascular dysfunction. We conducted a cross-sectional study of 100 participants, recruited from the University of Louisville Clinics. Endothelial function was assessed by calculating the reactive hyperemia index (RHI). Oxidative stress was indexed by measuring urinary levels of isoprostanes (n = 91). Inflammatory biomarkers were measured in the plasma (n = 80). Daily average PMlevels were obtained from regional monitoring stations. Adjusted associations between PMlevels and measured outcomes were tested using generalized linear models. The average age of participants was 48 years (44% male, 62% white); 52% had a diagnosis of hypertension, and 44% had type-2 diabetes. A 12.4% decrease in RHI was associated with 10 μg/mincrease in PM(95% CI: 21.0, -2.7). The F-2 isoprostane metabolite showed a positive association of 28.4% (95% CI: 2.7, 60.3) per 10 μg/mincrease in PM. Positive associations were observed with angiopoietin 1 (17.4%; 95% CI: 2.8, 33.8), vascular endothelial growth factor (10.4%; 95% CI: 0.6, 21.0), placental growth factor (31.7%; 95% CI: 12.2, 54.5), intracellular adhesion molecule-1 (24.6%; 95% CI: 1.6, 52.8), and matrix metalloproteinase-9 (30.3%; 95% CI: 8.0, 57.5) per 10 μg/mincrease in PM. Additionally, a 10 μg/mincrease in PMwas associated with 15.9% decrease in vascular cell adhesion molecule-1 (95% CI: 28.3, -1.3). These findings suggest that exposure to PMis associated with impaired vascular function, which may result from oxidative stress and inflammation, thereby leading to a pro-atherogenic state.

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PMID: 

Environ Health. 2019 Dec 30 ;18(1):117. Epub 2019 Dec 30. PMID: 31888649

Abstract Title: 

Atrial fibrillation hospitalization is associated with exposure to fine particulate air pollutants.

Abstract: 

BACKGROUND: Although air pollutants have been associated with cardiopulmonary mortality, their effects on the occurrence of atrial fibrillation (Afib) remain unclear. This study examined the association between ambient air pollutants and Afib occurrence.METHODS: Using a representative sample from the National Health Insurance Database of Taiwan, we applied a case-crossover study design to explore the associations between air pollutants and patients hospitalized with Afib from 2006 to 2011. The event day was when a patient was hospitalized with Afib, and the control days were the same days of the following weeks of the same month. The association between Afib occurrence and levels of ambient air pollutants (including particulate matter [PM] 2.5 PM, NO, SO, and O) was examined after adjusting for temperature and relative humidity. A two-pollutant model was used to examine the effect of the second pollutant when the first pollutant was determined to be significantly related to Afib.RESULTS: During 2006-2011, 670 patients hospitalized with the first onset of Afib were identified. The occurrence of Afib was associated with PM, in which a 22% (95% confidence interval = 3-44%) increase was related to an interquartile range increase (26.2 μg/m3) on the same day and a 19% (95% confidence interval = 0-40%) increase on the second day. A two-pollutant model was applied, and the results indicated that the effect of PMwas significantly associated with the occurrence of Afib. Patients aged over 65 years with DM and with hyperlipidemia were more susceptible to the effect of PM.CONCLUSIONS: In conclusion, the occurrence of Afib was associated with short-term exposure to fine particulate air pollutants in the general population.

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PMID: 

BMJ. 2019 12 30 ;367:l6572. Epub 2019 Dec 30. PMID: 31888884

Abstract Title: 

Association between ambient fine particulate pollution and hospital admissions for cause specific cardiovascular disease: time series study in 184 major Chinese cities.

Abstract: 

OBJECTIVE: To estimate the risks of daily hospital admissions for cause specific major cardiovascular diseases associated with short term exposure to ambient fine particulate matter (aerodynamic diameter≤2.5 μm; PM) pollution in China.DESIGN: National time series study.SETTING: 184 major cities in China.POPULATION: 8 834 533 hospital admissions for cardiovascular causes in 184 Chinese cities recorded by the national database of Urban Employee Basic Medical Insurance from 1 January 2014 to 31 December 2017.MAIN OUTCOME MEASURES: Daily counts of city specific hospital admissions for primary diagnoses of ischaemic heart disease, heart failure, heart rhythm disturbances, ischaemic stroke, and haemorrhagic stroke among different demographic groups were used to estimate the associations between PMand morbidity. An overdispersed generalised additive model was used to estimate city specific associations between PMand cardiovascular admissions, and random effects meta-analysis used to combine the city specific estimates.RESULTS: Over the study period, a mean of 47 hospital admissions per day (standard deviation 74) occurred for cardiovascular disease, 26 (53) for ischaemic heart disease, one (five) for heart failure, two (four) for heart rhythm disturbances, 14 (28) for ischaemic stroke, and two (four) for haemorrhagic stroke. At the national average level, an increase of 10μg/min PMwas associated with a 0.26% (95% confidence interval 0.17% to 0.35%) increase in hospital admissions on the same day for cardiovascular disease, 0.31% (0.22% to 0.40%) for ischaemic heart disease, 0.27% (0.04% to 0.51%) for heart failure, 0.29% (0.12% to 0.46%) for heart rhythm disturbances, and 0.29% (0.18% to 0.40%) for ischaemic stroke, but not with haemorrhagic stroke (-0.02% (-0.23% to 0.19%)). The national average association of PMwith cardiovascular disease was slightly non-linear, with a sharp slope at PMlevels below 50μg/m, a moderate slope at 50-250μg/m, and a plateau at concentrations higher than 250μg/m. Compared with days with PMup to 15μg/m, days with PMof 15-25, 25-35, 35-75, and 75μg/mor more were significantly associated with increases in cardiovascular admissions of 1.1% (0 to 2.2%), 1.9% (0.6% to 3.2%), 2.6% (1.3% to 3.9%), and 3.8% (2.1% to 5.5%), respectively.According to projections, achieving the Chinese grade 2 (35μg/m), Chinese grade 1 (15μg/m), and World Health Organization (10μg/m) regulatory limits for annual mean PMconcentrations would reduce the annual number of admissions for cardiovascular disease in China. Assuming causality, which should be done with caution, this reduction would translate into an estimated 36 448 (95% confidence interval 24 441 to 48 471), 85 270 (57 129 to 113 494), and 97 516 (65 320 to 129 820), respectively.CONCLUSIONS: These data suggest that in China, short term exposure to PMis associated with increased hospital admissions for all major cardiovascular diseases except for haemorrhagic stroke, even for exposure levels not exceeding the current regulatory limits.

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PMID: 

BMJ. 2019 12 30 ;367:l6720. Epub 2019 Dec 30. PMID: 31888885

Abstract Title: 

Long term exposure to ambient fine particulate matter and incidence of stroke: prospective cohort study from the China-PAR project.

Abstract: 

OBJECTIVE: To study the effect of long term exposure to ambient fine particulate matter of diameter≤2.5 μm (PM) on the incidence of total, ischemic, and hemorrhagic stroke among Chinese adults.DESIGN: Population based prospective cohort study.SETTING: Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project carried out in 15 provinces across China.PARTICIPANTS: 117 575 Chinese men and women without stroke at baseline in the China-PAR project.MAIN OUTCOME MEASURES: Incidence of total, ischemic, and hemorrhagic stroke.RESULTS: The long term average PMlevel from 2000 to 2015 at participants' residential addresses was 64.9μg/m, ranging from 31.2μg/mto 97.0μg/m. During 900 214 person years of follow-up, 3540 cases of incident stroke were identified, of which 63.0% (n=2230) were ischemic and 27.5% (n=973) were hemorrhagic. Compared with the first quarter of exposure to PM(78.2μg/m) had an increased risk of incident stroke (hazard ratio 1.53, 95% confidence interval 1.34 to 1.74), ischemic stroke (1.82, 1.55 to 2.14), and hemorrhagic stroke (1.50, 1.16 to 1.93). For each increase of 10μg/min PMconcentration, the increased risks of incident stroke, ischemic stroke, and hemorrhagic stroke were 13% (1.13, 1.09 to 1.17), 20% (1.20, 1.15 to 1.25), and 12% (1.12, 1.05 to 1.20), respectively. Almost linear exposure-response relations between long term exposure to PMand incident stroke, overall and by its subtypes, were observed.CONCLUSIONS: This study provides evidence from China that long term exposure to ambient PMat relatively high concentrations is positively associated with incident stroke and its major subtypes. These findings are meaningful for both environmental and health policy development related to air pollution and stroke prevention, not only in China, but also in other low and middle income countries.

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PMID: 

PLoS Med. 2019 Dec ;16(12):e1003010. Epub 2019 Dec 31. PMID: 31891579

Abstract Title: 

Ambient particulate matter pollution and adult hospital admissions for pneumonia in urban China: A national time series analysis for 2014 through 2017.

Abstract: 

BACKGROUND: The effects of ambient particulate matter (PM) pollution on pneumonia in adults are inconclusive, and few scientific data on a national scale have been generated in low- or middle-income countries, despite their much higher PM concentrations. We aimed to examine the association between PM levels and hospital admissions for pneumonia in Chinese adults.METHODS AND FINDINGS: A nationwide time series study was conducted in China between 2014 and 2017. Information on daily hospital admissions for pneumonia for 2014-2017 was collected from the database of Urban Employee Basic Medical Insurance (UEBMI), which covers 282.93 million adults. Associations of PM concentrations and hospital admissions for pneumonia were estimated for each city using a quasi-Poisson regression model controlling for time trend, temperature, relative humidity, day of the week, and public holiday and then pooled by random-effects meta-analysis. Meta-regression models were used to investigate potential effect modifiers, including cities' annual-average air pollutants concentrations, temperature, relative humidity, gross domestic product (GDP) per capita, and coverage rates by the UEBMI. More than 4.2 million pneumonia admissions were identified in 184 Chinese cities during the study period. Short-term elevations in PM concentrations were associated with increased pneumonia admissions. At the national level, a 10-μg/m3 increase in 3-day moving average (lag 0-2) concentrations of PM2.5 (PM ≤2.5 μm in aerodynamic diameter) and PM10 (PM ≤10 μm in aerodynamic diameter) was associated with 0.31% (95% confidence interval [CI] 0.15%-0.46%, P

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PMID: 

Neuropsychiatr Dis Treat. 2019 ;15:3143-3153. Epub 2019 Nov 11. PMID: 31806980

Abstract Title: 

Treatment Of Magnesium-L-Threonate Elevates The Magnesium Level In The Cerebrospinal Fluid And Attenuates Motor Deficits And Dopamine Neuron Loss In A Mouse Model Of Parkinson's disease.

Abstract: 

Purpose: Epidemiology research has demonstrated that magnesium (Mg) deficiency is associated with a high incidence of Parkinson's disease (PD). It is known that the systemic administration of MgSOis not able to elevate the Mg concentration in cerebrospinal fluid (CSF). This study aims to verify the protective effect of magnesium-L-threonate (MgT) in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model.Methods: C57BL/6J mice were orally administered MgT or MgSOfor 4 weeks, and received MPTP in the third week. After analysis of open-field and rotarod tests on the last day, tyrosine hydroxylase (TH) immunopositive cells and protein levels were quantified in the substantia nigra pars compacta (SNpc) and striatum. The expression of inducible nitric oxide synthase (iNOS) level was evaluated. Mg concentration in serum and CSF was measured after oral administration of MgSOor MgT in normal mice. Mg concentration in the CSF was increased in the mice treated with MgT but not MgSO.Results: The total distance and mean speed in open-field tests, and the time spent on rotarod in the MgT group were increased, compared with MPTP group. The MgT treatment but not MgSOdose-dependently attenuated the loss of TH-positive neurons, and the reduction of the TH expression in the SNpc. The MgT treatment also inhibited the expression of iNOS as measured by immunohistochemistry and Western blots. Double-immunofluorescence staining of TH and iNOS showed iNOS-positive cells were collocalized for TH-positive cells.Conclusion: The treatment with MgT is associated with an increase of Mg in the CSF. MgT, rather than MgSO4, can significantly attenuate MPTP-induced motor deficits and dopamine (DA) neuron loss.

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PMID: 

J Nutr Biochem. 2019 Nov 26 ;77:108301. Epub 2019 Nov 26. PMID: 31825817

Abstract Title: 

Severe magnesium deficiency compromises systemic bone mineral density and aggravates inflammatory bone resorption.

Abstract: 

We sought to evaluate the effects of magnesium (Mg) intake deficiency on bone metabolism in rats with induced periodontal disease (PD). Holtzman rats were randomly divided into two groups: Control – animals fed a standard diet and test – animals fed a diet with 90% Mg deficiency. After 60 days on the diets, all animals received ligature on the lower left first molars to induce PD. Animals were euthanized after 30 days following ligature placement. Blood and urine were collected for determination of serum concentrations of Mg, calcium, osteocalcin (OCN), alkaline phosphatase and parathyroid hormone (PTH) by enzyme-linked immunosorbent assay, and the urinary concentration of deoxypyridinoline (DPD). Systemic bone mineral density (BMD), bone volume and architectural bone parameters were evaluated by micro-CT in L4 lumbar vertebrae and mandible. Tartrate-resistant acid phosphatase staining and immunohistochemical (IHC) analysis of inducible nitric oxide synthase (iNOS), Runt-related transcription factor 2 (RUNX2), CD86, CD80, proliferating cell nuclear antigen, vascular endothelial growth factor, OCN and osteopontin were investigated. Reverse-transcription polymerase chain reaction was employed to assess mRNA expression of receptor-activator of nuclear factor-kB ligand, osteoprotegerin (OPG) and interleukin (IL)-6. Mg deficiency was associated with higher concentrations of PTH and DPD, and significant decrease on both systemic and mandibular BMD, as well as greater severity of alveolar and trabecular bone loss. Significant increase in osteoclasts was observed in the test group with PD. IHC analysis showed significant increase in the expression of iNOS and decreased expression of OCN and RUNX2. Increased IL-6 mRNA and decreased OPG mRNA expressions were evidenced in the test group with PD. Mg deficiency caused systemic effects indicative of altered bone metabolism in the vertebrae and affected both immune and stromal cells, aggravating inflammatory bone resorption in the ligature-induced model of periodontitis.

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PMID: 

J Cancer. 2019 ;10(25):6431-6438. Epub 2019 Oct 19. PMID: 31772676

Abstract Title: 

Liensinine inhibited gastric cancer cell growth through ROS generation and the PI3K/AKT pathway.

Abstract: 

Liensinine, an isoquinoline alkaloid extracted from the seed embryo of Nelumbo nucifera Gaertn, has been shown to exhibit various phrenological effects, including anti‑cancer activity. The aim of this study is to investigate the effects and mechanisms of liensinine in human gastric cancer cells. In this study, we found liensinine can significantly inhibit gastric cancer cell proliferationand. Liensinine inducedgastric cancer cell apoptosis by increasing cleaved PARP, caspased 3 and caspased 9. Moreover, liensinine induced cycle arrest by downregulatingcyclinD1/cyclin‑dependent kinase4 and phosphorylated protein kinase B. Furthermore, we found liensinine increases ROS levels and inhibits the PI3K/AKT pathway. These data suggested that liensinine might represent a novel and effective agent against gastric cancer.

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PMID: 

Mol Biol Rep. 2019 Dec 11. Epub 2019 Dec 11. PMID: 31823124

Abstract Title: 

Protective effect of Nelumbo nucifera (Gaertn.) against HO-induced oxidative stress on H9c2 cardiomyocytes.

Abstract: 

Ischemic heart disease (IHD), a severe condition of myocardium facing impediment in the supply of basic needs for cellular metabolism is caused by atherosclerosis. Though statin drugs could control the use of surgery on IHD patients, the complete rehabilitation or prophylaxis can be achieved through herbal-based medicines viz. either in the form of crude extract or pure phytocompounds. In the present study, pretreatment with leaf extract of Nelumbo nucifera Gaertn. was investigated for cardioprotective activity-in vitro by mitigating HO-induced oxidative stress. Analysis such as estimation of antioxidants, lipid peroxidation, and DNA fragmentation assay revealed significant protective effect of plant extract on cardiomyocytes. Reactive oxygen species detection was done by using 2',7'-dichlorofluorescein diacetate, apoptosis detection with Acridine Orange/Ethidium Bromide and nuclear damage detection by diamidino-2-phenylindole which confirmed the protective effect of N. nucifera extract. In addition, gene expression studies of apoptotic regulatory genes (Bcl2 and Cas-9) resulted in significant protection of nucifera extract pretreated and maintained cells. To conclude, in vitro cardioprotective activity of N. nucifera against HOinduced oxidative stress was achieved at the concentration of 50 µg/ml. Therefore, major phytocompounds present in extract could be beneficial in managing cardiac complications in the future.

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