Zinc Deficiency Promotes Calcification in Vascular Smooth Muscle Cells Independent of Alkaline Phosphatase Action and Partly Impacted by Pit1 Upregulation.

Inorganic phosphate (Pi) is a critical determinant of calcification, and its concentration is regulated by alkaline phosphatase (ALP) and Pit1. ALP is a key regulator of osteogenic calcification and acts by modulating local inorganic phosphate (Pi) concentrations through hydrolyzing pyrophosphate in the extracellular matrix (ECM). Pit1, a sodium-dependent phosphate transporter, regulates calcification via facilitating phosphate uptake within the cells. To investigate whether zinc differentially regulates osteoblastic and vascular calcifications, we examined ALP activity and Pit1 in osteoblastic and vascular smooth muscle cells (VSMCs). Our findings demonstrate that calcification in osteoblastic MC3T3-E1 cells is decreased via diminished ALP action under zinc deficiency. In contrast, zinc-deficiency-induced calcification in VSMCs is independent of ALP action, as demonstrated by very weak ALP activity and expression in calcified VSMCs. In zinc-deficient A7r5 VSMC, P accumulation increased with increasing Na phosphate concentration (3-7 mM) but not with ß-GP treatment, which requires ALP activity to generate Pi. Ca deposition also increased with Na phosphate in a dose-dependent manner; in contrast, ß-GP did not affect Ca deposition. In osteoblastic cells, Pit1 expression was not affected by zinc treatments. In contrast, Pit1 expression is highly upregulated in A7r5 VSMC under zinc deficiency. Using phosphonoformic acid, a competitive inhibitor of Pit1, we showed that calcification is inhibited in both A7r5 and MC3T3-E1 cells, indicating a requirement for Pit1 in both calcifications. Moreover, the downregulation of VSMC markers under zinc deficiency was restored by blocking Pit1. Taken together, our results imply that zinc-deficiency-induced calcification in VSMC is independent of ALP action in contrast to osteoblastic calcification. Moreover, Pit1 expression in VSMCs is a target for zinc deficiency and may mediate the inhibition of VSMC marker expression under zinc deficiency.

Ellagic Acid Prevented Dextran-Sodium-Sulfate-Induced Colitis, Liver, and Brain Injury through Gut Microbiome Changes.

Inflammatory bowel disease (IBD) affects millions of people worldwide and is considered a significant risk factor for colorectal cancer. Recent in vivo and in vitro studies reported that ellagic acid (EA) exhibits important antioxidant and anti-inflammatory properties. In this study, we investigated the preventive effects of EA against dextran sulfate sodium (DSS)-induced acute colitis, liver, and brain injury in mice through the gut-liver-brain axis. Acute colitis, liver, and brain injury were induced by treatment with 5% (w/v) DSS in the drinking water for 7 days. Freshly prepared EA (60 mg/kg/day) was orally administered, while control (CON) group mice were treated similarly by daily oral administrations with a vehicle (water). All the mice were euthanized 24 h after the final treatment with EA. The blood, liver, colon, and brain samples were collected for further histological and biochemical analyses. Co-treatment with a physiologically relevant dose (60 mg/kg/day) of EA for 7 days significantly reduced the DSS-induced gut barrier dysfunction; endotoxemia; and inflammatory gut, liver, and brain injury in mice by modulating gut microbiota composition and inhibiting the elevated oxidative and nitrative stress marker proteins. Our results further demonstrated that the preventive effect of EA on the DSS-induced IBD mouse model was mediated by blocking the NF-κB and mitogen-activated protein kinase (MAPK) pathway. Therefore, EA co-treatment significantly attenuated the pro-inflammatory and oxidative stress markers by suppressing the activation of NF-κB/MAPK pathways in gut, liver, and brain injury. These results suggest that EA, effective in attenuating IBD in a mouse model, deserves further consideration as a potential therapeutic for the treatment of inflammatory diseases.

Plum-Derived Exosome-like Nanovesicles Induce Differentiation of Osteoblasts and Reduction of Osteoclast Activation.

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 µg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.

The Effect of Apple-Derived Nanovesicles on the Osteoblastogenesis of Osteoblastic MC3T3-E1 Cells.

Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5 µg/mL apple NVs-treated group. In addition, the concentrarion of mineralized nodules was significantly increased in the apple NVs-treated groups. Furthermore, apple NVs increased the expression of the genes and proteins associated with osteoblast growth and differentiation, such as Runx2, ALP, OPN, and BMP2/4, which further activated ERK- and JNK-related mitogen-activated protein kinase signaling. These results demonstrate that apple NVs have a potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells through regulating the BMP2/Smad1 pathways.

Issues pertaining to Mg, Zn and Cu in the 2020 Dietary Reference Intakes for Koreans.

In the current years, it has now become necessary to establish standards for micronutrient intake based on scientific evidence. This review discusses issues related to the development of the 2020 Dietary Reference Intakes for Koreans (KDRI) for magnesium (Mg), zinc (Zn), and copper (Cu), and future research directions. Following issues were encountered when establishing the KDRI for these minerals. First, characteristics of Korean subjects need to be applied to estimate nutrient requirements. When calculating the estimated average requirement (EAR), the KDRI used the results of balance studies for Mg absorption and factorial analysis for Zn, which is defined as the minimum amount to offset endogenous losses for Zn and Mg. For Cu, a combination of indicators, such as depletion/repletion studies, were applied, wherein all reference values were based on data obtained from other countries. Second, there was a limitation in that it was difficult to determine whether reference values of Mg, Zn, and Cu intakes in the 2020 KDRI were achievable. This might be due to the lack of representative previous studies on intakes of these nutrients, and an insufficient database for Mg, Zn, and Cu contents in foods. This lack of database for mineral content in food poses a problem when evaluating the appropriateness of intake. Third, data was insufficient to assess the adequacy of Mg, Zn, and Cu intakes from supplements when calculating reference values, considering the rise in both demand and intake of mineral supplements. Mg is more likely to be consumed as a multi-nutrient supplement in combination with other minerals than as a single supplement. Moreover, Zn-Cu interactions in the body need to be considered when determining the reference intake values of Zn and Cu. It is recommended to discuss these issues present in the 2020 KDRI development for Mg, Zn, and Cu intakes in a systematic way, and to find relevant solutions.

Plum Prevents Intestinal and Hepatic Inflammation in the Acute and Chronic Models of Dextran Sulfate Sodium-Induced Mouse Colitis.

SCOPE: Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a chronic recurrent inflammatory disease of the digestive tract and increases the risk of colon cancer. METHOD AND RESULTS: This study evaluates the effects of dietary intervention with freeze-dried plum (FDP), a natural antioxidant and anti-inflammatory fruit with no toxicity on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in a mouse model and studies the molecular mechanisms of protection through the gut-liver axis. The results show that FDP decreases the levels of inflammatory mediators, which is a nitrative stress biomarker in both acute and chronic models. FDP markedly reduces DSS-induced injury to the colonic epithelium in both acute and chronic models. In addition, FDP significantly decreases the levels of pro-oxidant markers such as CYP2E1, iNOS, and nitrated proteins (detected by anti-3-NT antibody) in DSS-induced acute and chronic colonic injury models. Furthermore, FDP markedly reduces markers of liver injury such as serum ALT/AST, antioxidant markers, and inflammatory mediators in DSS-induced acute and chronic colonic injury. CONCLUSION: These results demonstrate that the FDP exhibits a protective effect on DSS-induced acute and chronic colonic and liver injury through the gut-liver axis via antioxidant and anti-inflammatory properties.

Depletion of Zinc Causes Osteoblast Apoptosis with Elevation of Leptin Secretion and Phosphorylation of JAK2/STAT3.

Zinc (Zn) has been reported to mediate leptin secretion, and thus leptin can be an important candidate molecule linking Zn with bone formation. The present study investigated whether zinc deficiency induces leptin secretion by activating a JAK2/STAT3 signaling pathway and leads to osteoblastic apoptosis. MC3T3-E1 cells were incubated for 24 h in normal osteogenic differentiation medium (OSM) or OSM treated with either 1 µM (Low Zn) or 15 µM (High Zn) of ZnCl2 containing 5 µM TPEN (Zn chelator). Our results demonstrated that low Zn stimulated extracellular leptin secretion and increased mRNA and protein expression of leptin in osteoblastic MC3T3-E1 cells. The OB-Rb (long isoform of leptin receptor) expressions were also elevated in osteoblasts under depletion of Zn. Leptin-signaling proteins, JAK2 and p-JAK2 in the cytosol of low Zn osteoblast conveyed leptin signaling, which ultimately induced higher p-STAT3 expression in the nucleus. Apoptotic effects of JAK2/STAT3 pathway were shown by increased caspase-3 in low Zn osteoblasts as well as apoptotic morphological features observed by TEM. Together, these data suggest that low Zn modulates leptin secretion by activating JAK2/STAT3 signaling pathway and induces apoptosis of osteoblastic MC3T3-E1 cells.

Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress.

Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.

Yam (Dioscorea batatas) Root and Bark Extracts Stimulate Osteoblast Mineralization by Increasing Ca and P Accumulation and Alkaline Phosphatase Activity.

Yam (Dioscorea batatas) is widely consumed as functional food for health promotion mainly in East Asia countries. We assessed whether yam root (tuber) or bark (peel) extracts stimulated the activity of osteoblasts for osteogenesis. MC3T3-E1 cells (mouse osteoblasts) were treated with yam root extracts (water or methanol) (study I) or bark extracts (water or hexane) (study II) within 0~10 µg/mL during the periods of osteoblast proliferation (5~10 day), matrix maturation (11~15 day) and mineralization (16~20 day) as appropriate. In study I, both yam root water and methanol extracts increased cell proliferation as concentration-dependent manner. Cellular collagen synthesis and alkaline phosphatase (ALP) activity, both the indicators of bone matrix protein and inorganic phosphate production for calcification respectively, were also increased by yam root water and methanol extract. Osteoblast calcification as cell matrix Ca and P accumulation was also increased by the addition of yam root extracts. In study II, yam bark extracts (water and hexane) increased osteoblast proliferation and differentiation, as collagen synthesis and ALP activity and osteoblast matrix Ca and P deposition. The study results suggested that both yam root and bark extracts stimulate osteogenic function in osteoblasts by stimulating bone matrix maturation by increasing collagen synthesis, ALP activity, and matrix mineralization.

Zinc Restored the Decreased Vascular Smooth Muscle Cell Viability under Atherosclerotic Calcification Conditions.

Zinc is considered to be involved in maintaining healthy vascular condition. Atherosclerotic calcification of vascular smooth muscle cells (VSMCs) occurs via the mechanism of cell death; therefore, cell viability is a critical factor for preventing VSMC calcification. In this study, we tested whether zinc affected VSMC viability under both normal physiological non-calcifying (0 mM P) and atherosclerotic calcifying conditions (3 and 5 mM P), since VSMC physiological characters change during the VSMC calcification process. The study results showed that an optimal zinc level (15 µM) restored the decreased VSMC viability which was induced under low zinc levels (0 and 1 µM) and calcifying conditions (3 and 5 mM P) at 9 and 15 days culture. This zinc-protecting effect for VSMC viability is more prominent under atherosclerotic calcifying condition (3 and 5 mM P) than normal condition (0 mM P). Also, the increased VSMC viability was consistent with the decreased Ca and P accumulation in VSMC cell layers. The results suggested that zinc could be an effective biomineral for preventing VSMC calcification under atherosclerotic calcifying conditions.

Functions and mechanisms of green tea catechins in regulating bone remodeling.

Osteoporosis is caused by an imbalance in bone remodeling, a process involving bone-building osteoblasts and bone-resorptive osteoclasts. Excessive reactive oxygen species and inflammatory responses have been shown to stimulate differentiation and function of osteoclasts while inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation via extracellular signal-regulated kinases (ERK), ERK-dependent nuclear factor-κB and Wnt/ß-catenin signaling pathways. The anti-oxidant and anti-inflammatory green tea catechins (GTC) have been shown to promote osteoblastogenesis, suppress osteoclastogenesis and stimulate the differentiation of mesenchymal stem cells into osteoblasts rather than adipocytes by modulating the signaling pathways. This paper reviews the pharmacokinetics and metabolism of GTC, their bone-protective activities evidenced in in vitro and in vivo studies, and the limited clinical studies supporting these preclinical findings. In light of the physical, economical, and social burdens due to osteoporosis, easily accessible and affordable preventive measures such as GTC deserves further clinical studies prior to its clinical application.

Plasma zinc's alter ego is a low-molecular-weight humoral factor.

Mild dietary zinc deprivation in humans and rodents has little effect on blood plasma zinc levels, and yet cellular consequences of zinc depletion can be detected in vascular and other tissues. We proposed that a zinc-regulated humoral factor might mediate the effects of zinc deprivation. Using a novel approach, primary rat vascular smooth muscle cells (VSMCs) were treated with plasma from zinc-deficient (<1 mg Zn/kg) or zinc-adequate (35 mg Zn/kg, pair-fed) adult male rats, and zinc levels were manipulated to distinguish direct and indirect effects of plasma zinc. Gene expression changes were analyzed by microarray and qPCR, and incubation of VSMCs with blood plasma from zinc-deficient rats strongly changed the expression of >2500 genes, compared to incubation of cells with zinc-adequate rat plasma. We demonstrated that this effect was caused by a low-molecular-weight (∼2-kDa) zinc-regulated humoral factor but that changes in gene expression were mostly reversed by adding zinc back to zinc-deficient plasma. Strongly regulated genes were overrepresented in pathways associated with immune function and development. We conclude that zinc deficiency induces the production of a low-molecular-weight humoral factor whose influence on VSMC gene expression is blocked by plasma zinc. This factor is therefore under dual control by zinc.

Marginal dietary zinc deficiency in vivo induces vascular smooth muscle cell apoptosis in large arteries.

AIMS: Dietary zinc deficiency has been associated with the development of atherosclerosis although the effects on vascular smooth muscle cells (VSMCs), important in maintaining atherosclerotic plaque integrity, are unknown. The main aim of this study was to elucidate the effect of a zinc-deficient environment on VSMCs using an in vivo model. METHODS AND RESULTS: Rats were maintained for 2 weeks on a marginally zinc-deficient diet which resulted in a significant reduction in plasma zinc levels. Large arteries from zinc-deficient rats had significantly increased apoptosis within the VSMC layers compared with arteries from rats on a zinc-adequate diet. This apoptosis occurred in parallel with a known apoptotic pathway, namely dephosphorylation of the pro-apoptotic protein Bcl-2-associated death promoter protein (BAD). Activation of extracellular signal-regulated kinase (ERK)1/2, which maintains BAD phosphorylation as a pro-survival mechanism, was decreased in arteries from zinc-deficient rats. The mechanisms of this in vivo effect were investigated in vitro. Cultured rat VSMCs incubated with plasma from zinc-deficient rats similarly resulted in increased apoptosis in parallel with BAD dephosphorylation and decreased ERK1/2 activation. Further related apoptotic mechanisms induced by plasma from zinc-deficient rats involved a prolonged rise in [Ca²âº]i leading to subsequent activation of the phosphatase calcineurin. Calcineurin activation was required to dephosphorylate BAD. In addition, an increase in oxidative stress contributed to the apoptotic effect induced by plasma from zinc-deficient rats. CONCLUSION: In conclusion, a marginally zinc-deficient diet is pro-apoptotic for VSMCs and this may contribute to cardiovascular disease.

Long-term zinc deprivation accelerates rat vascular smooth muscle cell proliferation involving the down-regulation of JNK1/2 expression in MAPK signaling.

BACKGROUND: The accelerated proliferation of vascular smooth muscle cells (VSMCs) is a contributor for atherosclerosis by thickening the vascular wall. Since zinc modulation of VSMC proliferation has not been clarified, this study investigated whether zinc affects VSMC proliferation. METHODS AND RESULTS: Both a rat aorta origin vascular smooth muscle cell line (A7r5 VSMCs) and primary VSMCs which were collected from rat aorta (pVSMCs) were cultured with zinc (0-50 µM Zn) for short- (≤12 d) and long-term (28 d) periods under normal non-calcifying (0 or 1 mM P) or calcifying (>2 mM P) P conditions. Mouse vascular endothelial cells (MS I cells) were also cultured (under 0-50 µM Zn and 10 mM P for 20 d) to compare with VSMC cultures. While during short-term culture of VSMCs, zinc deprivation decreased cell proliferation in a zinc-concentration manner both under non-calcifying and calcifying conditions in A7r5 and pVSMCs (P < 0.05), during long-term cultures (28 d), A7r5 VSMC proliferation was inversely related to medium zinc concentration under normal physiological P conditions (regression coefficient r(2) = -0.563, P = 0.012). The anti-cell proliferative effect of zinc supplementation (>50 µM) was VSMC-specific. Long-term (35 d), low zinc treatment down-regulated JNK expression and activation, while not affecting ERK1/2 MAPK signaling in A7r5 VSMCs. CONCLUSION: The results showed that chronic zinc deprivation accelerated VSMC proliferation, perhaps due to down-regulation of MAPK-JNK signaling, and that the anti-cell proliferative role of zinc is VSMC-specific. The findings suggested that zinc may have anti-VSMC proliferative properties in atherosclerosis.

The contents of heavy metals (cd, cr, as, pb, ni, and sn) in the selected commercial yam powder products in South Korea.

Yam (Dioscorea) has long been used as foods and folk medicine with the approved positive effects for health promotion. Although consumption of yam products is increasing for health promotion, reports for the metal contamination in commercial yam powder products to protect the consumers are lacking. In this study, we aimed to assess whether the commercial yam powder products were heavy metal contaminated or not using the yam products from six commercial products from various places in South Korea. The contents of heavy metals (Cd, Cr, As, Pb, Ni, and Sn) in yam powder products were measured and compared to national and international food standard levels. Also, the metal contamination was monitored during the food manufacturing steps. The study results showed that the contents of heavy metals (Cd, Cr, As, and Pb) in yam powder products are similar to those in national 'roots and tubers' as well as in various crops. In comparison to three international standard levels (EU, Codex and Korea), Cd content in yam powder products was lower but Pb content was 5 times higher. Also, Pb, Ni, and Sn may have the potential to be contaminated during food manufacturing steps. In conclusion, the level of heavy metals (Cd, Cr, As, Ni, and Sn) except Pb is considered relatively safe on comparison to national and international food standard levels.

Phosphate-induced rat vascular smooth muscle cell calcification and the implication of zinc deficiency in a7r5 cell viability.

The calcification of vascular smooth muscle cells (VSMCs) is considered one of the major contributors for vascular disease. Phosphate is known as the inducer for VSMC calcification. In this study, we assessed whether phosphate affected cell viability and fetuin-A, a calcification inhibitor protein, both which are related to VSMC calcification. Also, VSMC viability by zinc level was assessed. The results showed that phosphate increased Ca and P deposition in VSMCs (A7r5 cell line, rat aorta origin). This phosphate-induced Ca and P deposition was consistent with the decreased A7r5 cell viability (P<0.05), which implies phosphate-induced calcification in A7r5 cells might be due to the decreased VSMC cell viability. As phosphate increased, the protein expression of fetuin-A protein was up-regulated. A7r5 cell viability decreased as the addition of cellular zinc level was decreased (P<0.05). The results suggested that zinc deficiency causes the decreased cell viability and it would be the future study to clarify how zinc does act for VSMC cell viability. The results suggest that the decreased VSMC viability by high P or low Zn in VSMCs may be the risk factor for vascular disease.

Fruits and dietary phytochemicals in bone protection.

Osteoporosis is a disease of bone characterized by loss of bone matrix and deterioration of bone microstructure that leads to an increased risk of fracture. Cross-sectional studies have shown a positive association between higher fruit intake and higher bone mineral density. In this review, we evaluated animal and cellular studies of dried plum and citrus and berry fruits and bioactive compounds including lycopene, phenolics, favonoids, resveratrol, phloridzin, and pectin derived from tomato, grapes, apples, and citrus fruits. In addition, human studies of dried plum and lycopene were reviewed. Animal studies strongly suggest that commonly consumed antioxidant-rich fruits have a pronounced effect on bone, as shown by higher bone mass, trabecular bone volume, number, and thickness, and lower trabecular separation through enhancing bone formation and suppressing bone resorption, resulting in greater bone strength. Such osteoprotective effects seem to be mediated via antioxidant or anti-inflammatory pathways and their downstream signaling mechanisms, leading to osteoblast mineralization and osteoclast inactivation. In future studies, randomized controlled trials are warranted to extend the bone-protective activity of fruits and their bioactive compounds. Mechanistic studies are needed to differentiate the roles of phytochemicals and other constitutes in bone protection offered by the fruits. Advanced imaging technology will determine the effective doses of phytochemicals and their metabolites in improving bone mass, microarchitecture integrity, and bone strength, which is a critical step in translating the benefits of fruit consumption on osteoporosis into clinical data.

Zinc isotope ratio imaging of rat brain thin sections from stable isotope tracer studies by LA-MC-ICP-MS.

Zinc stable isotope tracers (67Zn and 7°Zn) were injected into rats at two different time points to investigate the feasibility of using tracers to study zinc kinetics at the microscale within distinct tissue features. Laser ablation coupled to multi-collector ICP-MS was used to analyse average isotope ratios in liver thin sections and to generate bio-images showing zinc isotope ratio distribution in brain thin sections. Average isotope ratios of all samples from treated animals were found to be statistically different (P < 0.05) from samples from untreated control animals. Furthermore, differing isotope ratios in physiological features of the brain, namely hippocampus, amygdala, cortex and hypothalamus, were identified. This indicates that these regions differ in their zinc metabolism kinetics. While cortex and hypothalamus contain more tracer two days after injection than 14 days after injection, the opposite is true for hippocampus and amygdala. This study showed that stable isotope tracer experiments can be combined with laser ablation MC-ICP-MS to measure trace element kinetics in tissues at a microscale level.

Suboptimal dietary zinc intake promotes vascular inflammation and atherogenesis in a mouse model of atherosclerosis.

SCOPE: Cardiovascular health is strongly influenced by diet. Zinc has antioxidant and anti-inflammatory properties but its long-term influence on vascular health at dietary intake levels relevant to the human population in developed countries has not been studied. We investigated the influence of suboptimal zinc intake in a Western-type diet on the development of vascular inflammation and arterial plaque in apoE knock-out (AEKO) mice. METHODS AND RESULTS: Weanling AEKO and wild-type (WT) controls were given high saturated fat (21% w/w) and high cholesterol (0.15%) semi-synthetic diets containing 3 or 35 mg Zn/kg (AEKO and WT) or 8 mg Zn/kg (AEKO only) for over 6 months. AEKO mice on zinc intakes of 3 and 8 mg Zn/kg (suboptimal zinc) developed significantly (p < 0.05) more aortic plaque than AEKO mice consuming 35 mg Zn/kg (adequate zinc). Circulating levels of interleukin-1ß, interleukin-6 and soluble vascular adhesion molecule-1 were significantly (p < 0.05) raised at the lowest zinc intake in AEKO mice, as compared to zinc-adequate controls. Plasma total cholesterol and total protein were also significantly (p < 0.05) increased at the lowest zinc intake. CONCLUSION: We propose that suboptimal dietary zinc intake raises circulating pro-atherogenic lipoprotein levels that promote vascular inflammation and enhance arterial plaque formation.

Dietary polyphenols and mechanisms of osteoarthritis.

Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms.