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.

[The Role of Vitamin D3 on the Immune Responses of Monocytes]. / Vitamin D3'ün Monositlerin Immün Yaniti Üzerindeki Rolü.

The active form of vitamin D (Vit D), 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), is important for cell functions and immunity, as well as its role in bone metabolism. Monocytes/macrophages initiate innate immune response, and is considered to be the cell that first comes into contact with the pathogen. They play effective roles in innate immune and inflammatory responses by intercellular relations and inflammatory mediator secretion. Human THP-1 leukemia cells are frequently used for the in vitro determination of the signal pathways, and the functions of monocyte/macrophages. Nuclear factor-kappa B (NF-κB) are complex networks of signaling pathways that regulate many important cellular behaviors, especially in inflammation, cell death, cell differentiation or proliferation. Midkine (MK) is a cytokine and growth factor that is one of the regulators of inflammatory processes, immune cell functions, proliferation and autoimmunity. The effects of Vit D3 on inflammation and MK secretion in hyperglycemia is still unknown. In this study, it was aimed to determine the dose-dependent effects of Vit D3 on the lipopolysaccharide (LPS) stimulated pro/ anti-inflammatory cytokine, NF-κB and MK responses of THP-1 monocyte cells under normo and hyperglycemic conditions. For this purpose, THP-1 monocyte cells stimulated with LPS (Escherichia coli, 0111, 1 µg/ml) under normoglycemic (glucose 100 mg/dl)/hyperglycemic (glucose 500 mg/dl) conditions, were incubated for 24 hours in the presence and absence of 10-50-100 IU/ml Vit D3. MK, TNF-α, IL-8, IL-10 cytokine levels in the supernatants collected from the wells at the end of the incubation periods, and NF-κB levels in the obtained cell lysates were detected by ELISA method. LPS stimulation induced higher levels of TNF-α, IL-8 and MK responses in hyperglycemic conditions. IL-10 secretions were found to be decreased under hyperglycemia. Vit D3 modulates TNF-α, IL-10 and MK secretions in hyperglycemic conditions. The MK and TNF-α levels were determined to be correlated with NF-κB and IL-10. The results obtained in the study showed that Vit D3 can play a role in immune modulation by regulating NF-κB and cytokine/ chemokine-like molecule MK suppression and proinflammatory/anti-inflammatory cytokine balance. The mechanism of the action of Vit D3 under different conditions should be examined in detail.

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 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.

Antioxidant effects of vitamin D on lacrimal glands against high dose radioiodine-associated damage in an animal model.

PURPOSE: To evaluate antioxidant effects of active vitamin D (calcitriol) against high-dose radioiodine (RAI) therapy-associated damage of lacrimal gland. MATERIALS AND METHODS: Wistar albino rats were used and divided into three groups randomly (n = 12/group). The first group was appointed as the negative control group and received no RAI or medication. The second group was appointed as the positive control group that only received 3 mCi/kg (111 MBq/kg) RAI via gastric gavage and the last group was the treatment group that received 3 mCi/kg RAI via same method and calcitriol (200 ng/kg/day) via intraperitoneal administration. Seven days after RAI administration, bilateral intraorbital (IG), extraorbital (EG) and Harderian (HG) glands were removed for the evaluations of histopathologic, tissue cytokine, total oxidant status (TOS) and total antioxidant status (TAS). RESULTS: RAI led to significant increase in tissue TOS, TNF-α, IL-6 levels and significant decrease in IL-10 and TAS levels (p < 0.05 for each). Addition of adjunctive calcitriol reversed all these parameters significantly (p < 0.05 for each).The following histopathologic parameters were seen more frequently in positive control group than the other groups: Abnormal lobular pattern, perivascular infiltration, periductal infiltration, lipofuscin-like accumulation, acinar atrophy, periductal and periacinar fibrosis in all lacrimal gland types (p < 0.05), acinar fibrosis in EG (p = 0.049), periductal fibrosis in EG and HG (p = 0.049 and 0.038, respectively), abnormal cell outlines in EG and HG (p = 0.020 and 0.011, respectively) and variation in cell size in the IG and the HG (p = 0.003 and 0.049 respectively). CONCLUSIONS: RAI caused significant oxidative stress and inflammation in lacrimal glands. Vitamin D demonstrated potent anti-inflammatory, antioxidant and radio-protective effects on lacrimal glands in histopathologic, tissue cytokine and oxidant/antioxidant level evaluations.

Serum nitric oxide levels in patients with coronary artery ectasia.

OBJECTIVE: Serum levels of nitric oxide (NO) are decreased in patients with atherosclerosis and also are a risk factor for the development of atherosclerosis. Endothelial dysfunction and diffuse atherosclerosis have been proposed for the etiology of coronary artery ectasia (CAE). The purpose of this clinical trial was to determine the relationship between CAE and serum NO levels. METHODS: This prospective controlled study was conducted between January 2008 and March 2012. Serum levels of NO were compared in 40 patients with CAE (mean age 60.1±7.3 years) and 40 patients with normal coronary arteries (mean age 57.6±5 years) as a control group. CAE was diagnosed when a segment of coronary artery was more than 1.5 times the diameter of the adjacent healthy segment. Patients with stenotic atherosclerotic plaques, slow coronary flow, previous history of revascularization, acute coronary syndromes, left ventricular dysfunction, valvular heart disease, and systemic diseases were not included in the study. The effect of NO on the outcome was studied by constructing a receiver operating characteristic (ROC) curve with CAE as the primary variable. Effects of different variables on CAE were calculated using binary logistics regression analysis. RESULTS: Serum NO concentrations were significantly lower in patients with CAE than in the control group (42.1±20.1 µmol/L vs. 77.3±15.7 µmol/L, p<0.001). According to the results of the multivariate regression analysis, LDL and NO levels were identified as independent factors associated with CAE (OR=1.02, 95% CI 1-1.04, p=0.02 and OR=0.88, 95% CI 0.83-0.93, p=0.001, respectively). ROC analysis revealed that using a cut-off point of 63.3, NO level predicts CAE with a sensitivity of 87.5% and specificity of 90%. CONCLUSION: Our study indicates that decreased levels of NO are present in patients with CAE compared to patients with normal coronary arteries, supporting the hypothesis that decreased levels of NO might be associated with CAE development.