A review of key challenges of electrospun scaffolds for tissue‐engineering applications

Tissue engineering holds great promise to develop functional constructs resembling the structural organization of native tissues to improve or replace biological functions, with the ultimate goal of avoiding organ transplantation. In tissue engineering, cells are often seeded into artificial structures capable of supporting three‐dimensional (3D) tissue formation. An optimal scaffold for tissue‐engineering applications should mimic the mechanical and functional properties of the extracellular matrix (ECM) of those tissues to be regenerated. Amongst the various scaffolding techniques, electrospinning is an outstanding one which is capable of producing non‐woven fibrous structures with dimensional constituents similar to those of ECM fibres. In recent years, electrospinning has gained widespread interest as a potential tissue‐engineering scaffolding technique and has been discussed in detail in many studies. So why this review? Apart from their clear advantages and extensive use, electrospun scaffolds encounter some practical limitations, such as scarce cell infiltration and inadequate mechanical strength for load‐bearing applications. A number of solutions have been offered by different research groups to overcome the above‐mentioned limitations. In this review, we provide an overview of the limitations of electrospinning as a tissue‐engineered scaffolding technique, with emphasis on possible resolutions of those issues. Copyright © 2015 John Wiley & Sons, Ltd.     

β-Thalassemia Mutations in the Iranian Kurdish Population of Kurdistan and West Azerbaijan Provinces

The aim of this study was to investigate the prevalence and spectrum of β-thalassemia (β-thal) mutations in the population of Sunni Muslim Kurds in western Iran and to set up a prenatal diagnostic laboratory. Sixty unrelated Kurdish β-thal patients identified in hematology clinics from different cities were studied. The mutations in 120 chromosomes were studied by polymerase chain reaction–amplification refractory mutation system and direct sequencing methods. We found fifteen β-thal mutations, and IVS-II-1 (G>A) was the most frequent, comprising 35%?of all mutations. Other common mutations were frameshift codons 8/9 (+G) 15.7%, IVS-I-1 (G>A) 8%, FSC 5 (–CT) 6.7%, FSC 8 (–AA) 6.7%, and IVS-I-110 (G>A) 6%. This is the first comprehensive study in this region and could provide a reference for prenatal testing and genetic counseling in this population.     

Prognostic risk factors for early diagnosing of Preeclampsia in Nulliparas

Background:

Preeclampsia is of major complications of pregnancy that is associated with maternal morbidity and mortality. Therefore, prediction and early diagnosis of preeclampsia would be helpful for better controlling of related complications. Our study aimed to investigate risk factors helping to predict and early diagnose of preeclampsia.

Materials and Methods:

A total of 739 nulliparous women at their 24-28^th weeks of the first pregnancy were enrolled in this multi-center cohort study. Incidence or absence of preeclampsia in this population was evaluated up to the end of pregnancy period. For each case, a record sheet was assigned that contained information about haematocrit level in weeks 24-28^th of pregnancy, blood pressure, result of roll-over test in weeks 24-28^th of pregnancy and the presence of disease up to end of the study. Diagnosis of preeclampsia was made based on gold standard.

Results:

Overall, 3.9 % of all cases developed preeclampsia. The mean maternal age, body mass index (BMI), years of education and positive roll-over test were significantly higher in preeclampsia group (P < 0.001). However, the mean gestational age and changes in the levels of haematocrit were significantly higher in normotensive cases (P < 0.001). Our combined model could predict preeclampsia with a sensitivity of 93% and a specificity of 80%.

Conclusion:

Simple combined model of demographic characteristics including maternal age, BMI, years of education and positive roll-over tests can predict preeclampsia without any cost for the patients.     

Autoimmune neutropenia of infancy

Neutrophil antibodies were demonstrated in 119 of 121 infants and young children with chronic neutropenia, establishing the diagnosis of autoimmune neutropenia of infancy. The median age at diagnosis was 8 months (range 3 to 30 months), and the female/male ratio was 6:4. Autoimmune neutropenia of infancy was manifested by recurrent fever and infection. All patients had selective neutropenia (absolute neutrophil count 0 to 500), and many had monocytosis. Fifteen of 16 patients tested failed to respond to epinephrine and hydrocortisone stimulation. Bone marrow had myeloid hyperplasia and reduced mature neutrophils. Recovery occurred in all 81 patients who passed the age of 5 years, except for one patient who is recovering at 6 1/2 years. The median age at recovery was 30 months; 95% recovered before 4 years. The estimated median duration of disease was 20 months. Neutrophil antibodies were detected early in the neutropenic phase by a combination of immunofluorescence and agglutination tests. Ten percent of these antibodies had specificity for NA1 or NA2. Ten of the 12 serum samples with a strong reaction in the flow cytometer reacted only with neutrophils. Two also reacted with an unidentified subpopulation (30%) of lymphocytes. Lymphocyte subsets were normal in 10 patients investigated, and abnormal levels of circulating immune complexes were detected in sera from 11 of 25 (44%) patients tested. Temporary remission was induced in all of eight patients who received intravenous IgG therapy. Autoimmune neutropenia of infancy is probably the most common cause of chronic neutropenia in infancy and early childhood, can be diagnosed by immunologic techniques, and requires only conservative management; spontaneous cure appears to be the rule.     

Effects of metformin on autoimmune immunoglobins and interferon-γ in patients with early diagnosed pemphigus vulgaris: a prospective clinical trial

The management of pemphigus vulgaris (PV) is challenging. This study aimed to evaluate the immunomodulating effects of metformin on PV. The study was conducted in two phases: in the first phase, patients received routine first-line treatment (prednisolone plus azathioprine) for 2 months, then in the second phase, metformin was added to this regimen for another 2 months. After addition of metformin to the first-line medications, significant reductions were seen in serum IgG1 (reduced from 534.92 ± 134.83 mg/dL to 481.58 ± 130.46 mg/dL, P < 0.001), IgG4 (51.83 ± 27.26 mg/dL to 44.50 ± 26.05 mg/dL, P < 0.001) and interferon-γ (277.99 ± 108.71 pg/mL to 45.05 ± 17.080 pg/mL, P = 0.03) concentrations. The suppressant effect of metformin was greatest on IgG4 (coefficient of variation 1.28), the dominant subclass of IgG involved in PV. Metformin could have immunomodulating effects on PV with controlling effects on steroid complications.     

Production and characterization of cytotoxic Thy-1 antibody-secreting hybrid cell lines. Detection of T cell subsets.

Responses to Thy-1 were used as a model system to examine parameters which affect the production of antibody-secreting lines derived from somatic cell hybridization. Experiments with the Thy-1.1 response revealed that the frequency of clones producing Thy-1.1 antibodies is a constant of 4 to 6% for each 10000 plaque-forming cells (PFC) input in the fusion cell mixture, regardless of the maturational stage of the response. Therefore, PFC responses to Thy-1 were optimized by studying variables in the choice and dose of antigen, the response kinetics and in the fusion procedures. Thus, to produce Thy-1.1 antibody-secreting cell lines, we used (a) spleen cells at the peak of the PFC response, (b) xenogeneic (rat) rather than allogeneic donors, (c) secondary rather than primary responses and (d) high ratios of NS-1 to spleen cells. For the reproducible production of Thy-1.2 antibody-secreting hybridomas, PFC responses to Thy-1.2 were similarly optimized in AKR mice. Response kinetics and antigen dose were shown to be very critical parameters. By varying the number of cells used for priming, it was revealed that doses only slightly higher than optimal produced a dramatic hyporesponsiveness in the subsequent secondary response. Using the above information, hybrid lines secreting antibody to Thy-1.2 were obtained reproducibly and one line, F7D 5, which secretes a cytotoxic IgM antibody was characterized in detail since a monoclonal antibody may differ from conventional antisera for immunochemical and genetic reasons. Serologically, F7D 5 Thy-1.2 antibody was found to behave as a conventional Thy 1.2 alloantiserum, At high dilutions however, the antibody can be used to discriminate long-lived T cells (adult thymectomized mice) from newly produced T cells (antilymphocyte antiserum-treated mice). Functionally, in numerous T cell-dependent assays both in vivo and in vitro, including helper, suppressor and cytotoxic T cell functions as well as responses to mitogens and antigens, the F7 D 5 antibody behaved as a potent and absolute T cell-depleting agent. This cell line and some anti-Thy-l.1 producing lines are available for research purposes.