The aim of this meta-analysis was to investigate whether the blood concentrations of patients with multiple sclerosis (MS) are associated with those of the healthy control group in terms of trace elements including zinc (Zn), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), and copper (Cu). A comprehensive search was performed in online databases including PubMed, Scopus, Embase, and Web of Science for studies, which have addressed trace elements in MS up to July 23, 2020. The chi-square test and I 2 statistic were utilized to evaluate inter-study heterogeneity across the included studies. Weighted mean differences (WMDs) and corresponding 95% CI were considered as a pooled effect size (ES). Twenty-seven articles (or 32 studies) with a total sample comprised of 2895 participants (MS patients (n = 1567) and controls (n = 1328)) were included. Pooled results using random-effects model indicated that the levels of Zn (WMD = − 7.83 mcg/dl, 95% CI = − 12.78 to − 2.87, Z = 3.09, P = 0.002), and Fe (WMD = − 13.66 mcg/dl, 95% CI = − 23.13 to − 4.19, Z = 2.83, P = 0.005) were significantly lower in MS patients than in controls. However, it was found that levels of Mn (WMD = 0.03 mcg/dl, 95% CI = 0.01 to 0.04, Z = 2.89, P = 0.004) were significantly higher in MS patients. Yet, no significant differences were observed in the levels of Mg, Se, and Cu between both groups. This meta-analysis revealed that the circulating levels of Zn and Fe were significantly lower in MS patients and that Mn level was significantly higher than those in the control group. However, it was found that there was no significant difference between MS patients and controls with regard to levels of Mg, Se, and Cu.

The present meta-analysis was performed to assess the association between MS patients and control subjects in terms of their circulating levels of arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd). We searched Medline/PubMed, Scopus, Web of Science, and Embase up until June 2020 to identify all studies that examined the concentrations of heavy metals in MS patients. Statistical tests used to assess inter-study heterogeneity were Cochrane's Q test and the I 2 statistic. Given the observed significant heterogeneity, the random-effects model was employed to pool the weighted mean differences (WMDs) and the corresponding 95 % confidence intervals (CIs). Out of a total of 1181 articles, 16 studies with 1650 participants (772 patients with MS and 878 controls) were included in this review meta-analysis. Pooled results using random-effects model showed that the levels of Pb (WMD= 0.73 µg/L, 95 % CI= 0.33 to 1.12, P< 0.001), As (WMD= 2.48 μg/L, 95 % CI= 1.44 to 3.53, P <0.001; I 2 = 98.9 %, P <0.001), and Cd (WMD= 0.17 μg/L, 95 % CI= 0.09 to 0.26, P <0.001) were significantly higher in MS patients than those of the controls. However, there were no significant differences in the levels of Hg (WMD= -0.14 µg/L, 95 % CI= -0.77 to 0.49, P= 0.658) among both groups. Sensitivity analysis indicated that after excluding one-by-one study, the overall pooled WMD of Pb was changed. This meta-analysis showed that patients with MS had significantly higher levels of circulatory As and Cd compared to the controls. Yet, there was no statistically significant difference between circulating levels of Hg and Pb among MS patients and controls. See also Figure 1 (Fig. 1) .

Background The present systematic review and meta-analysis aimed to ascertain if the circulating levels of apelin, as an important regulator of the cardiovascular homeostasis, differ in patients with cardiovascular diseases (CVDs) and controls. Methods A comprehensive search was performed in electronic databases including PubMed, Scopus, EMBASE, and Web of Science to identify the studies addressing apelin in CVD up to April 5, 2021. Due to the presence of different units to measure the circulating levels of apelin across the included studies, they expressed the standardized mean difference (SMD) and their 95% confidence interval (CI) as summary effect size. A random-effects model comprising DerSimonian and Laird method was used to pool SMDs. Results Twenty-four articles (30 studies) comprised of 1793 cases and 1416 controls were included. Pooled results obtained through random-effects model indicated that apelin concentrations in the cases’ blood samples were significantly lower than those of the control groups (SMD = -0.72, 95% CI: -1.25, -0.18, P = 0.009; I2 = 97.3%, P<0.001). New combined biomarkers showed a significant decrease in SMD of apelin/high-density lipoprotein cholesterol (apelin/HDL-C) ratio [-5.17; 95% CI, -8.72, -1.63, P = 0.000; I2 = 99.0%], apelin/low-density lipoprotein cholesterol (apelin/LDL-C) ratio [-4.31; 95% CI, -6.08, -2.55, P = 0.000; I2 = 98.0%] and apelin/total cholesterol (apelin/TC) ratio [-17.30; 95% CI, -22.85, -11.76, P = 0.000; I2 = 99.1%]. However, no significant differences were found in the SMD of apelin/triacylglycerol (apelin/TG) ratio in cases with CVDs compared to the control group [-2.96; 95% CI, -7.41, 1.49, P = 0.000; I2 = 99.2%]. Conclusion The association of apelin with CVDs is different based on the region and disease subtypes. These findings account for the possible usefulness of apelin as an additional biomarker in the diagnosis of CVD in diabetic patients and in the diagnosis of patients with CAD. Moreover, apelin/HDL-c, apelin/LDL-c, and apelin/TC ratios could be offered as diagnostic markers for CVD.

This systematic review and meta-analysis were conducted to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with breast cancer (BC) in Asians. Systematic searches were conducted in PubMed, EMBASE, Web of Science, and Scopus by May 2020. Interstudy heterogeneity was also assessed with a Q test, along with I 2 statistics. Random-effects models were applied to pooled crude ORs with corresponding 95% CIs for the genetic models. A total of 1097 identified results, along with 36 qualified studies were included: for MTHFR C677T polymorphism, a total of 36 studies was comprised of 11,261 cases and 13,318 controls and for MTHFR A1298C polymorphism, a number of 19 studies contained 7424 cases and 8204 controls. Likewise, for C677T polymorphism, an increased risk of BC was seen for the allelic (OR 1.21,

Overexpression of recombinant proteins in Escherichia coli results in inclusion body formation, and consequently decreased production yield and increased production cost. Co-expression of chaperon systems accompanied by recombinant protein is a general method to increase the production yield. However, it has not been successful enough due to imposed intense stress to the host cells. The aim of this study was to balance the rate of protein production and the imposed cellular stresses using a two-step expression system. For this purpose, in the first step, green fluorescent protein (GFP) was expressed as a recombinant protein model under control of the T7-TetO artificial promoter-operator, accompanied by Dnak/J/GrpE chaperon system. Then, in the next step, TetR repressor was activated automatically under the control of the stress promoter ibpAB and suppressed the GFP production after accumulation of inclusion bodies. Thus in this step incorrect folded proteins and inclusion bodies are refolded causing increased yield and solubility of the recombinant protein and restarting GFP expression again. Total GFP, soluble and insoluble GFP fractions, were measured by Synergy H1 multiple reader. Results showed that expression yield and soluble/insoluble ratio of GFP have been increased 5 and 2.5 times using this system in comparison with the single step process, respectively. The efficiency of this system in increasing solubility and production yield of recombinant proteins was confirmed. The two-step system must be evaluated for expression of various proteins to further confirm its applicability in the field of recombinant protein production.