Modulatory Role of Macrophage Migration Inhibitory Factor on Cytokines and Clinical Features of Sarcoidosis

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology with a significant heterogeneity in organ manifestations, severity, and clinical course. Subjects with sarcoidosis share several features such as, non-necrotizing granuloma, hypergammaglobulinemia, increased local and circulating inflammatory cytokines, such as interleukin (IL)-6, IL-18, and interferon gamma (IFN-γ). Macrophage migration inhibitory factor (MIF) is a pluripotent chemokine produced by various cell types. The expression of MIF at sites of inflammation suggests a regulatory role in the function of macrophages. The objective of this study was to investigate the role of MIF in the serum and bronchoalveolar lavage (BAL) fluid of sarcoidosis patients in association with clinical features and other cytokines. Methods: Sera and BALs of sarcoidosis patients (n=55) were collected at the time of diagnosis and patients were followed longitudinally for 3 years. Additionally, fifteen healthy controls participated in the study. The medical records of all patients including, demographics, radiography stages, pulmonary function tests, and organ involvements were recorded. The levels of MIF, IL-18, IL-10, IL-6, IFN-γ and lysozyme in serum and BAL samples were measured by ELISA. Statistical analyses were performed using SPSS software. Results: Serum MIF had a remarkable positive correlation with IL-10 and IFN-γ but had a negative correlation with serum IgG levels. Importantly, longitudinal follow-up showed a positive correlation between MIF and % predicted diffusion capacity (%DLCO) at 3-year. Serum IL-18 had a significant positive correlation with serum lysozyme, but a negative correlation with % predicted total lung capacity at 3-year follow up. We identified two groups of sarcoidosis subjects with distinct clinical and cytokine features. A group with prominent extrapulmonary involvement, and low serum MIF, IL-10 and IFN-γ levels and a group with elevated serum MIF, IL-10 and IFN-γ levels. Moreover, we found a negative correlation between BAL IL-18 and BAL MIF in sarcoidosis subjects.Conclusions: Patients with low serum MIF, IL-10 and IFN-γ levels has severe and mostly extrapulmonary sarcoidosis with elevated lysozyme and IL-18 levels. Our work provides understanding of phenotypic diversity in association with heterogeneity in cytokine landscape in sarcoidosis.

The relationship between genetic variants associated with primary ovarian insufficiency and lipid profile in women recruited from MASHAD cohort study

Background and aim Primary Ovarian Insufficiency (POI) is defined by the occurrence of menopause before the age of 40 years. It is often associated with cardiovascular disease (CVD). The purpose of this study was to explore the relationship between POI-associated genotypes cardiometabolic disorder risk factors. Methods One hundred seventeen women with POI and one hundred eighty-three healthy women without POI were recruited in this study. DNA was extracted and analyzed using ASO-PCR or Tetra ARMS-PCR. Lipid profiles were also assessed. Results Multivariate logistic regression analysis showed that individuals with GG vs. TT genotype of the rs1046089 SNP were more likely to have a higher serum LDL (p = 0.03) compared to the control group. There was also a significant association between low serum HDL and rs2303369 and rs4806660 SNP genotypes in the POI group. In the POI group, the percentage of those with high total cholesterol was lower in those with a CC genotype compared to those with a TT genotype (p = 0.03). Conclusion Some SNPs reported to be associated with POI appear to be independently associated with dyslipidemia. These results may be helpful to identify subjects with POI who may be susceptible to CVD.

Low Serum Iron Status Is Associated With Low Incidence of Coronary Artery Disease In Women

Background: Disorders of iron metabolism has been implicated in cardiovascular disease. However, the association of serum ferritin and coronary artery disease (CAD) remains inconsistent. Here, we investigated the associations of serum iron metabolism with the incidence of CAD, the severity of coronary artery stenosis, metabolic biomarkers, and 1-year restenosis after coronary artery revascularization. Methods: A total of 643 CAD patients and 643 healthy controls were enrolled to assess the associations of serum iron status with the presence of CAD, the severity of CAD, and 1-year rehospitalization after revasculation. Serum iron metabolism and other metabolic markers were measured in all subjects. All statistical analyses were analyzed using SPSS22.0 software and STATA statistical package.Results: Serum level of iron metabolism markers, including serum iron, ferritin, unsaturated transferrin iron binding capacity (UIBC), Total iron binding capacity (TIBC) levels, in CAD groups was significantly higher than the control group (P<0.001). UIBC and TIBC were negatively correlated with ferritin in both sexes. Serum level of iron (OR=0.806, 95% CI (0.687-0.944), UIBC (OR=0.919, 95% CI (0.852-0.992), and TIBC (OR=0.864, 95% CI (0.787-0.95) were found to have a protective role for CAD in women (P<0.05, Table 3). The OR for ferritin was significant in the both sexes (OR=1.029, 95% CI (1.002-1.058) in men, OR=1.02, 95% CI (1.005-1.034) in women, P<0.05). Conclusion: Low Serum level of iron, UIBC, TIBC and ferritin levels were found to have a protective role for CAD in women, but not in men. Elevated serum ferritin is independently and positively associated with CAD in men and women.

The Synergy Beteeen Diurnal Temperature Range and Calcium Concentration Help to Predict Hospital Mortality in Patients with Acute Myocardial Infarction

Epidemiological studies have suggested that cold is an important contributor to acute cardiovascular events and mortality. However, little is known about the Diurnal Temperature Range(DTR)impact on mortality of the patients with myocardial infarction.Calcium ions(Ca2+)play a vital role in the human body, such as cardiac electrophysiology and contraction.To investigate whether DTR on admission moderates the association between serum calcium and in-hospital mortality in patients with acute myocardial infarction(AMI). This retrospective study enrolled consecutive adult patients with AMI at a single center in China (2003–2012). Patients were divided into four groups (Ca-Q1–4) according to serum calcium concentration quartiles. Multivariate logistic regression modeling was used to assess whether DTR moderated the association between serum calcium and in-hospital mortality. The predictive value of serum calcium was evaluated by receiver operating characteristic (ROC) curve and net reclassification improvement (NRI) analyses.The study included 3780 patients.In-hospital mortality was 4.97%(188/3780).DTR moderated the association between serum calcium and in-hospital mortality(P-interaction=0.020).Patients with low serum calcium in the highest DTR quartile exhibited an increased risk of in-hospital mortality(odds ratio for Ca-Q4 vs.Ca-Q1, 0.03;95%confidence interval[95%CI], 0.01–0.20;P for trend<0.001).In the highest DTR quartile, adding serum calcium concentration to the risk factor model increased the area under the ROC curve(0.81 vs.0.76;P<0.001)and increased NRI by 20.2%(95%CI 7.5–32.9;P=0.001).Low serum calcium was an independent risk factor for in-hospital mortality in patients with AMI, and this association was moderated by DTR.Careful attention should be paid to patients with low serum calcium who experience a higher DTR on admission.

Does serum progesterone level impact the ongoing pregnancy rate in frozen embryo transfer under artificial preparation with vaginal progesterone? Study protocol for a randomized controlled trial

Background In previous retrospective studies, low serum progesterone level on the embryo transfer day is associated with lower clinical pregnancy and ongoing pregnancy rates. Whether adding progesterone in low serum progesterone patients can rescue the outcome, there is no sufficient evidence from randomized controlled studies. Methods This trial is a clinical randomized controlled study (high serum progesterone vs low serum progesterone 1:1, 1:1 randomization ratio of intervention vs the control group with low serum progesterone). The eligible hormone replacement therapy—frozen embryo transfer (HRT-FET) cycles, will be recruited and randomly assigned to two parallel groups when serum progesterone is < 7.24μg/l on the day of embryo transfer for D3. The intervention group will be extrally given intramuscular progesterone 40 mg per day from D3 to 8 weeks of gestation if clinical pregnancy. The primary outcome is the ongoing pregnancy (beyond 12 weeks of gestation) rate. Discussion The findings of this study will provide strong evidence for whether the progesterone addition from the D3 in low serum progesterone patients can improve the outcome in the HRT-FET cycle. Trial registration ClinicalTrials.govNCT04248309. Registered on January 28, 2020