Expression of indoleamine 2,3-dioxygenase in dermal fibroblasts functions as a local immunosuppressive factor

As a possible way of making a non-rejectable skin substitute, here, we ask the question of whether the expression of indoleamine 2,3-dioxygenase (IDO) selectively suppresses immune, but skin, cell proliferation. To address this question, a series of experiments in which adenovirus (Ad-IDO) infected IDO expressing dermal fibroblasts were co-cultured with different types of immune cells were carried out. The immune cells were then harvested and evaluated for propidium iodide (PI) positive cells by FACS analysis. TUNEL assay was also carried out to determine the apoptotic status of these cells. The results showed that the expression of IDO in dermal fibroblasts significantly induces apoptotic death of PBMC, CD4(+)-, CD8(+)- and B cell-riched primary lymphocytes, Jurkat cells, and THP-1 cells. IDO-mediated damage of immune cells was restored by an addition of tryptophan and IDO inhibitor. Using the same approaches, we also demonstrated that skin cells and endothelial cells are remarkably resistant to tryptophan-deficient environment. Furthermore, no significant difference in cell proliferation between Ad-GFP (control)- and Ad-IDO-GFP-infected either keratinocytes or fibroblasts, was found. The results of this study, therefore, suggest that the expression of IDO by dermal fibroblasts mediates immune cell damage and this may shed a new light toward developing a non-rejectable skin substitute in the future.     

Predictors of mental and physical health in non-cirrhotic patients with viral hepatitis: A case control study

ObjectiveTo identify independent predictors of mental and physical health in patients with viral hepatitis.MethodsHepatitis C (HCV) and hepatitis B (HBV) infected patients, and community control subjects with equal age and sex distribution were recruited. All subjects filled in personal characteristics questionnaire, Hospital Anxiety and Depression Scale (HADS), Iowa Fatigue Scale (IFS), and Medical Outcomes Survey Short Form-12 (SF-12). All patients had measurement of routine laboratory values, and some had recent liver biopsy. Regression analyses were used to identify predictors of physical and mental health.ResultsOne hundred eighty nine subjects (162 males, 27 females, for each group N = 63) with mean (± SD) age of 39 ± 11 years were included. Anxiety and depression were important predictors of SF-12 (and its subscales MCS and PCS) and IFS scores, whereas IFS scores independently predicted HADS, PCS, MCS, and SF-12 scores. After controlling for confounders, HCV infection was independently associated with impairment of physical health. Moreover, creatinine showed an inverse strong relation with fatigue. Genotype 3a of HCV was independently associated with depressed and anxious states, whereas higher inflammation grade was significantly related to depression. Marital status, non-psychiatric comorbidities, and history of alcohol abuse also predicted health scores in the patients. Adjusted R²s for linear models were 0.571 to 0.709, whereas areas under the receiver operating characteristic (ROC) curve for logistic models were 0.90 to 0.93.ConclusionIn viral hepatitis patients, besides mental and medical comorbidities, marital status, and alcohol abuse, HCV infection itself is associated with impaired physical and possibly mental health.     

A safe postero-medial approach to posterior cruciate ligament avulsion fracture

The posterior cruciate ligament (PCL) plays a major role in knee stabilization, and clinical studies have shown an increase in incidence of its injury. Due to the surrounding neurovascular elements in the popliteal space, open approaches to repair such injury are difficult to perform. The “safe postero-medial approach” to PCL avulsion fracture is a simple approach, does not require exploration of the neurovascular elements, and produced satisfactory results in the majority of patients.     

Interleukin-10 gene polymorphisms and susceptibility to brucellosis in Iranian patients

Background: Interleukin-10 (IL-10) is a Th2-type cytokine that inhibits macrophage activation. It is known that production of IL-10 is affected by its gene promoter polymorphisms. Objective: To investigate the relationship between IL-10 gene promoter polymorphisms and susceptibility to brucellosis. Methods: One hundred and ninety patients with brucellosis and 81 healthy animal husbandmen who owned infected animals and consumed their contaminated dairy products were included in this study. All individuals were genotyped for three bi-allelic IL-10 gene promoter polymorphisms at positions -1082(G/A), -819(T/C), and -592(A/C) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The distribution of C alleles at positions -592 and -819 of IL-10 were significantly higher in patients than in the healthy animal husbandmen (p=0.034 and p=0.0086, respectively). IL-10 ATA single and double haplotypes were significantly higher in controls, compared to the patients (p= 0.0278 and p=0.013, respectively). Conclusion: According to the results higher frequency of C alleles at positions -592 and -819 of IL-10 in patients may be considered as genetic factors for susceptibility to brucellosis.     

Folate metabolism genes, vegetable intake and renal cancer risk in central Europe

In a multicenter case-control study of renal cell carcinoma (RCC) conducted in central and eastern Europe, we reported a strong inverse association with high vegetable intake and RCC risk. The odds ratio (OR) for high compared to the lowest tertile of vegetable intake was OR = 0.67; (95% confidence interval (CI): 0.53-0.83; p-trend < 0.001). We hypothesized that variation in key folate metabolism genes may modify this association. Common variation in 5 folate metabolism genes (CBS: Ex9+33C > T (rs234706), Ex13 +41C > T (rs1801181), Ex18 -391 G > A (rs12613); MTHFR: A222V Ex5+79C > T (rs1801133), Ex8-62A > C (rs1801131); MTR: Ex26 20A > G (rs1805087), MTRR: Ex5+136 T > C (rs161870), and TYMS:IVS2-405 C > T (rs502396), Ex8+157 C > T (rs699517), Ex8+227 A > G (rs2790)) were analyzed among 1,097 RCC cases and 1,555 controls genotyped in this study. Having at least 1 variant T allele of MTHFR A222V was associated with higher RCC risk compared to those with 2 common (CC) alleles (OR = 1.44; 95% CI: 1.17-1.77; p = 0.001). After stratification by tertile of vegetable intake, the higher risk associated with the variant genotype was only observed in the low and medium tertiles (p-trend = 0.001), but not among those in the highest tertile (p-interaction = 0.22). The association remained robust after calculation of the false discovery rate (FDR = 0.05). Of the 3 TYMS SNPs examined, only the TYMS IVS2 -405 C (rs502396) variant was associated with a significantly lower risk compared to the common genotype (OR = 0.73; 95% CI: 0.57-0.93). Vegetable intake modified the association between all 3 TYMS SNPs and RCC risk (p-interaction < 0.04 for all). In summary, these findings suggest that common variation in MTHFR and TYMS genes may be associated with RCC risk, particularly when vegetable intake is low.     

Global Prevalence of Anemia in Pregnant Women: A Comprehensive Systematic Review and Meta-Analysis

Maternal and Child Health Journal - Anemia is one of the most critical health conditions affecting people worldwide. The disease is silent, with a slow progression and a few physical symptoms....     

The association between diabetic complications and health-related quality of life in patients with type 2 diabetes: a cross-sectional study from Iran

Quality of Life Research - This study aimed to investigate the health-related quality of life (HRQoL) of type 2 diabetic patients and its relationship with the complications of diabetes in...