Serum midkine level might be a diagnostic tool for COVID19 disease in pregnancy: From the disease severity, hospitalization and disease progression respects.

BACKGROUND: New biomarkers for diagnosis and monitoring the COVID-19 disease are the most important topics to be studied recently. We aimed to investigate the association between midkine levels and disease severity in pregnant women with COVID-19. METHODS: Totally 186 pregnant women were participated in this study. 96 of them were healthy pregnant women, 90 of them were pregnant women with COVID19. Pregnant women were evaluated according to their trimesters. Serum midkine level, biochemical profile clinical and disease severity outcomes of pregnant women were obtained. RESULTS: Our results showed that pregnant women with COVID19 have significantly increased serum midkine level compared to healthy pregnant women (1.801 ± 0.977 vs 0.815 ± 0.294 ng/dL). According to the data among each trimester, it was shown that there were significant increase in serum midkine level during all pregnancy trimesters (1st trimester Control Group: 0.714 ± 0.148, COVID-19 group 1.623 ± 0.824, p < 0.0001; 2nd trimester Control Group: 0.731 ± 0.261, COVID-19 group 2.059 ± 1.146, p < 0.0001; 3rd trimester Control Group: 1.0 ± 0.35, COVID-19 group 1.723 ± 0.907, p = 0.001). Serum midkine levels were significantly different between disease severity subgroups of pregnant women with COVID19; moderate and severe/critic groups had significantly higher serum midkine level than mild group. There was also significant correlation between serum midkine level and severity status (p:0.0001, r: 0.468). The most striking results of serum midkine levels were corelation between length of hospitalization (p: 0.01, r: 0.430) and O2 saturation (p < 0.0001, r: -0.521). ROC curve analysis showed that serum midkine level might be a tool for predicting COVID-19 in pregnant women with COVID-19 (AUC: 0.912, 95% CI: [0.871, 0.952], p < 0.0001) CONCLUSION: Our data showed that there is an obvious relation between COVID19 progression and serum midkine level for the first time which might be used for monitoring the disease process.

Evaluation of the safety and efficacy of AdvaxTM as an adjuvant: A systematic review and meta-analysis.

PURPOSE: Developing a vaccine with improved immunogenicity is still a growing priority for many diseases. Different types of adjuvants may be beneficial to initiate and maintain the long-lasting immunogenicity of vaccines. Evidence has shown that polysaccharide adjuvants are efficient in improving immunological mechanisms with their biocompatibility and biodegradability characteristics. In this study, we aimed to investigate the safety and efficacy of AdvaxTM an adjuvant derived from delta inulin. METHODS: A systematic research was performed in Pubmed, Web of Science, and Scopus databases for the following keywords; "AdvaxTM" OR "delta inulin" until December 14th, 2020. RevMan 5.4.1 software was used for cumulative meta-analysis and bias analysis. We also used GraphPad Prism 6 software for the figures. RESULTS: In the cumulative meta-analysis, it was found that seroconversion and geometric mean titers (GMT) levels significantly increased in AdvaxTM-adjuvanted group (mean difference: 12.31, 95% Cl [4.14, 20.47], p â€‹= â€‹0.003; 17.10, 95% Cl [4.35, 29.85], p â€‹= â€‹0.009, respectively). We also observed that AdvaxTM could be effective in improving immunogenicity by inducing T-cell responses and plasmablast generation in viral vaccines. CONCLUSIONS: In this study, it was shown that AdvaxTM is a safe and well-tolerated adjuvant. AdvaxTM could be a potent adjuvant in increasing the protection and immunogenicity of different vaccines without safety issues. However, further studies are needed to verify these effects of AdvaxTM adjuvant.

Maternal and Placental Zinc and Copper Status in Intra-Uterine Growth Restriction.

BACKGROUND AND AIM: Zinc and copper are essential trace elements for cell growth and proliferation. Their deficiency may contribute to intrauterine growth restriction (IUGR). We aimed to determine the zinc and copper status of maternal serum and placenta samples of pregnant women with fetal IUGR and age-matched pregnant women without IUGR. METHOD: Serum and placenta samples obtained from 37 IUGR and 21 healthy pregnant women were analyzed at delivery. RESULTS: Placenta zinc concentrations and placenta zinc/copper ratio were significantly lower in the IUGR group compared to controls (p < 0.05). Placenta zinc concentrations correlated with birth weight (p: 0.01, r: 0.31). Maternal levels of zinc and copper were similar between pregnant women with IUGR and controls. CONCLUSIONS: Lower placental zinc and zinc/copper ratio levels in pregnancies with IUGR may indicate that placenta zinc and placental zinc/copper status might be involved in IUGR.

Maternal selenium status plays a crucial role on clinical outcomes of pregnant women with COVID-19 infection.

Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID-19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID-19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second (p: .0003) and third (p: .001) trimesters with COVID-19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week (p < .0001, r: -.541), D-dimer (p: .0002, r: -.363) and interleukin-6 (IL-6) level (p: .02, r: -.243). In the second trimester, serum selenium level positively correlated with white blood cell (p: .002, r: .424), neutrophil (p: .006, r: .39), lymphocyte (p: .004, r: .410) count and hemoglobin (p: .02, r: .323), hematocrit (p: .008, r: .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte (p: .04, r: .353) and negatively correlated with C-reactive protein level (p: .03, r: -.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID-19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL-6 and D-dimer levels, which indicate selenium's role in disease progression.

The Effects of Zinc Supplementation on C-Reactive Protein and Inflammatory Cytokines: A Meta-Analysis and Systematical Review.

Zinc is known for anti-inflammatory and antioxidant roles. In this meta-analysis, we aim to evaluate the impact of zinc supplementation on inflammatory markers, acute-phase reactants, and serum zinc level during inflammatory and infectious diseases. PubMed, Scopus, and Web of Science databases were screened systematically with the terms "zinc supplementation" AND "CRP" OR "IL-1ß" OR "IL-2" OR "IL-6" OR "IL-10" OR "IL-12" OR "TNF-α" OR "TGF-ß" OR "IFN-γ" OR "WBC (clinical trial)" OR "macrophage (clinical trial)" OR "lymphocyte (clinical trial)" OR "neutrophil (clinical trial)" OR "virus (clinical trial)" OR "antiviral (clinical trial)" for all databases. A total of 2,258 publications were screened, and 73 articles had suitable data for the meta-analysis. Serum zinc level was significantly higher in supplementation group compared with controls [P = 0.0006, mean difference: 11.35 (4.84, 17.87)] (n = 37). Zinc supplementation downregulates acute-phase reactants, especially serum C-reactive protein (CRP) in adults [P < 0.00001, mean difference: -0.75 (-0.98, -0.52)] (n = 22) and pregnant women [FEM P < 0.00001, mean difference: -1.77 (-2.53, -1.00)] (n = 3) but not in children [REM P = 0.10, mean difference: -0.85 (-1.86, 0.17)] (n = 3). In subgroups analysis of chronic inflammatory diseases, serum CRP [REM P < 0.00001, mean difference: -0.57 (-0.76, -0.38)] were significantly lower in zinc-supplemented patients compared with no intervention group. Zinc supplementation (mg/day) correlated with serum interferon-gamma (IFN-γ) level (P = 0.018, r = 1,000). In the nonsupplemented group, serum zinc correlated with serum interleukin-6 (IL-6) level (P = 0.041, r = -0.829) and serum tumor necrosis factor alpha (TNF-α) level (P = 0.063, r = 0.730). Zinc intake correlated with serum zinc (P = 0.0428, r = 0.5115) and TNF-α (P = 0.0043, r = -0.9461). This meta-analysis shows that zinc supplementation improves CRP levels in adults and pregnant women. It might have modulatory effects on cytokine secretions and blood cells in inflammatory and infectious diseases. For the first time, we investigated the effects of zinc supplementation on inflammatory cytokine.

Is Zinc an Important Trace Element on Bone-Related Diseases and Complications? A Meta-analysis and Systematic Review from Serum Level, Dietary Intake, and Supplementation Aspects.

Bone-related diseases are very common problems, especially in the elderly population. Zinc takes part in the growth and maintenance of healthy bones. This meta-analysis aims to evaluate the effects of zinc supplementation or dietary zinc intake on serum zinc levels and bone turnover markers. A systematical research was performed with 2899 articles in PubMed, WoS, and Scopus for relevant articles in English which have mean/standard deviation values of serum zinc levels, dietary zinc intake/zinc supplementation (mg/day), and bone turnover markers up to February 2020. In the overall analysis, serum zinc level was significantly lower in patients with osteoporosis compared with controls (p 0.0002). Dietary zinc intake decreased in the fracture group compared with controls according to subgroup analysis patients with fracture (p 0.02). Zinc supplementation was effective on the femoral neck (p < 0.0001) and lumbar spine (p 0.05) bone mineral density (BMD). In the correlation analysis of the data obtained from all of the included studies, serum osteocalcin (p 0.0106, r - 0.9148) correlated with serum zinc level. In conclusion, serum zinc level and dietary zinc intake could have an essential role in preventing osteoporosis. Zinc supplementation might improve bone turnover markers for bone formation such as serum osteocalcin and serum alkaline phosphatase and also, BMD at the site of the femoral neck.

The Relation Between Trace Element Status (Zinc, Copper, Magnesium) and Clinical Outcomes in COVID-19 Infection During Pregnancy.

SARS CoV-2 is a novel coronavirus which has caused many deaths in the recent pandemic. This study aimed to determine zinc, copper and magnesium status on pregnant women with COVID-19. 100 healthy (33/32/35) and 100 SARS-CoV-2 positive (34/33/33) pregnant women were included in the study according to their trimesters. Blood samples were obtained from the patients along with the initial laboratory tests for clinical outcomes upon their first admission to hospital. In the first and third trimesters serum zinc level was lower (p:0,004 and p:0,02), serum copper level was higher (p:0,006 and p:0,008), the Zn / Cu ratio decreased(p < 0.0001 and p < 0.0001) and the serum magnesium level was higher(p < 0.0001 and p < 0.0001) in the COVID-19 group.In the second trimester COVID-19 patients had lower serum zinc (p:0,05) and copper levels (p:0,0003) compared to controls. Disease severity correlated with zinc/copper ratio in COVID19 patients (p:0.018, r:-0.243). Serum zinc and Zn/Cu ratio levels had a negative relationship with acute phase markers such as IL-6, Erythrocyte Sedimentation Rate, procalcitonin and C-reactive Protein. Also, increased serum magnesium level may play a role in decreased white blood cell, neutrophil, lymphocyte cell count and increased CRP levels in the third trimester. This study indicated that trace element status changed in pregnant women with COVID-19. The effect of trace elements on pregnant women diagnosed with COVID-19 infection was investigated in comparison with healthy pregnant women for the first time. This effect will be revealed better in more comprehensive studies to be planned in the future.

The relationship between frailty and serum alpha klotho levels in geriatric patients.

BACKGROUND: Frailty is a medical syndrome resulting in loss of endurance, strength and physiological function. There is insufficient data to understand the process of frailty formation at the gene level, however one of the product of Klotho gene known as an anti-aging gene with many functions that prolong lifespan is alpha klotho protein. We aimed to investigate the relationship between frailty and the serum alpha klotho protein levels. METHODS: In this cross-sectional analysis, there were 89 patients aged 65 years old and older, 45 of whom were frail and 44 of whom were not frail, were included in the study. Within the scope of the study, a sociodemographic and clinical information form, the Turkish version of the FRAIL scale and a comprehensive geriatric assessment were evaluated. In addition to routine laboratory tests, plasma alpha klotho protein levels were measured. RESULTS: The mean alpha klotho protein levels of the patients were 0.76 ± 1.01 ng/ml in the control group and 0.54 ± 0.61 ng/ml in the frail group, however, there was no statistically significant difference between the two groups (p = 0.286). C-reactive protein (CRP) levels were significantly higher and hemoglobin (Hb) levels were significantly lower in the frail patients compared to the control group (p < 0.05). It was observed that alpha klotho protein level was inversly correlated with increased CRP levels but association was weak (p = 0.022, R: -0.245). Hb levels (p = 0.018, R: 0.250) was weakly correlated with alpha klotho protein level. CONCLUSION: No significant relationship was found between frailty and alpha klotho protein levels in the geriatric patients. Further comprehensive studies are needed to explore this subject.

The Relationship Between Metabolic Syndrome Development and Tissue Trace Elements Status and Inflammatory Markers.

Insulin resistance, impaired glucose regulation, dyslipidemia, low-grade inflammation, and elevated blood pressure are main components of the metabolic syndrome (MetS). Trace elements, especially zinc (Zn) and copper (Cu) and cytokines, have physiological importance due to their presence in inflammatory processes and glucose metabolism. Therefore, this study aimed to investigate the potential relationship between cytokine responses and trace elements in different tissues of sucrose-induced MetS rats compared with healthy controls (n:7/groups). Tissue Zn concentrations are found to be decreased in the liver (p = 0.00) and pancreas (p < 0.01) and increased in the kidney (p = 0.00) and heart tissues (p < 0.001) of MetS group. Serum Zn levels were also found to be decreased in MetS compared with control group (p < 0.01), while there was any significant difference in serum Cu concentrations between groups. The Cu concentration (p < 0.01) was found decreased, and Zn/Cu ratio (p < 0.01) was found increased in kidney tissues. TNF-α, IL-6 levels were found increased in MetS tissues. With this study, the Zn and Cu concentrations and their relationships with inflammatory response in different tissues in MetS are reported for the first time in the literature. Serum and tissue Zn levels with diversities in distribution were found to have a higher impact on MetS pathogenesis than Cu levels. It has been concluded that there is a relationship between Zn and Cu concentrations and inflammatory marker levels in MetS pathophysiological mechanisms.

Serum zinc level and dietary zinc intake status in non-alcoholic fatty liver disease: A meta-analysis and systematic review.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a common health problem related to diet and a sedentary lifestyle. Zinc has essential roles in diabetes, insulin resistance and inflammation. This meta-analysis aims to evaluate the relationship between NAFLD and dietary zinc intake/serum zinc levels. Materials and Methods: A systematic search was performed in PubMed, Web of Science, and Scopus databases for relevant English articles with mean/standard deviation values of serum zinc levels (µg/dL) and dietary zinc intake (mg/day) up to February 2020. We screened "fatty liver disease" and "zinc" keywords; totally 864 articles, eight of them were found to have suitable serum zinc level or daily zinc intake data for meta-analysis. Results: Serum zinc level in NAFLD patients were lower than healthy controls (data from 984 individuals, FEM, p<0.00001). The meta-analysis results of the nutritional zinc intake of totally 19438 individuals were similar in NAFLD and control groups (FEM, p=0.36). Conclusion: Serum zinc levels were lower in NAFLD patients, even though they have similar zinc intake in the diet, which suggests that there may be an absorption problem or increased need, with a distributional disorder which results in lower serum zinc levels. Further studies need to evaluate the role of zinc in NAFLD.

Cord blood zinc status effects on pregnancy outcomes and its relation with maternal serum zinc levels: a systematic review and meta-analysis.

BACKGROUND: The association between maternal and cord blood zinc level and pregnancy outcomes remains uncertain. The present study aims to assess whether maternal blood zinc level represents cord blood zinc level correctly. METHODS: In this meta-analysis, systematic search was performed in PubMed, Web of Science, and Scopus databases for relevant available English articles which included mean and standard deviation values of cord blood zinc level up to April 2019. For the assessment of the relation between cord blood zinc level and pregnancy outcomes, the pooled standard mean difference with 95% confidence interval (CI) was used and 23 studies were analyzed. RESULTS: Cumulative analysis showed that cord blood zinc level was found significantly decreased in pregnancies with complications compared with healthy pregnancy controls [REM: P = 0.0007, mean difference - 7.9 (- 12.48, - 3.31)]. For further analysis, maternal serum zinc level status was determined from same studies to compare with cord blood levels and subgroups were detected as "Preterm", "Preeclampsia", "Small for gestational age/Intrauterine growth restriction and Low birth weight". It was observed that cord blood zinc levels in subgroup analysis were also decreased and/or tend to be decreased compared to healthy pregnancies, except for preeclampsia subgroup. Also, a correlation was seen between cord blood and maternal blood zinc level status (R = 0.4365, 95% CI - 0.530, 0.756; P = 0.0351). CONCLUSION: It was thought that cord blood zinc level might tend to decrease more than maternal serum zinc level in the pathological conditions during pregnancies.