Generation of neural stem cells from adult astrocytes by using a single reprogramming factor

Generating neural stem cells (NSCs) from astroglia as an abundant cell type in the mammalian brain has a promising outlook to be used in cell-replacement therapy for treatment of neurodegenerative disorders and neuronal trauma. However, little is known about a single reprogramming factor that may lead to the generation of induced NSCs (iNSCs) from adult brain-derived astrocytes in the absence of extrinsic inductive signals. Here, we show that zinc-finger nuclear protein Zfp521 alone is sufficient for converting the adult mouse brain-derived astrocytes into iNSCs. In vitro, Zfp521-iNSCs demonstrated long-term self-renewal and multipotency and expressed related markers. Moreover, single-seeded iNSCs were able to produce NSC colonies. These results suggest that application of Zfp521 to generate iNSCs could be regarded as a new approach for conversion of resident astrocytes into iNSCs in cell therapy for in vivo treatment of neural injuries.     

Mercury,Lead, Cadmium,and Barium Levels in Human Breast Milk and Factors Affecting Their Concentrations in Hamadan,Iran

Biological Trace Element Research - Breast milk is considered the best source of nutrition for all infants. However, exposure of newborns to toxic metals is of special interest due to their...     

Non-equilibrium molecular dynamics study on radial thermal conductivity and thermal rectification of graphene

In the present study, the radial thermal rectification and thermal conductivity of the graphene were investigated by non-equilibrium molecular dynamics simulation and then corrected by quantum correction to make it closer to the fact. The Optimised three-body Tersoff potential is employed in order to simulate the interactions between the carbon atoms in the graphene sheet. A circular region in the centre and the one at the graphene edge are selected as hot and cold bath to generate radial temperature gradient. It is observed that the heat current passes through radially inward direction than outward with the same temperature gradient and hence there is a radial thermal rectification in graphene. Also, temperature distribution and heat flux are theoretically introduced as a function of distance from the graphene centre and then it is confirmed by the molecular dynamics simulation data. Finally, the influence of temperature gradient and size of graphene on radial thermal rectification and the impact of size on the radial thermal conductivity is investigated.     

Huntington’s Disease and Mitochondrial DNA Deletions: Event or Regular Mechanism for Mutant Huntingtin Protein and CAG Repeats Expansion?!

The mitochondrial DNA (mtDNA) may play an essential role in the pathogenesis of the respiratory chain complex activities in neurodegenerative disorders such as Huntington's disease (HD). Research studies were conducted to determine the possible levels of mitochondrial defect (deletion) in HD patients and consideration of interaction between the expanded Huntingtin gene as a nuclear gene and mitochondria as a cytoplasmic organelle. To determine mtDNA damage, we investigated deletions based in four areas of mitochondrial DNA, in a group of 60 Iranian patients clinically diagnosed with HD and 70 healthy controls. A total of 41 patients out of 60 had CAG expansion (group A). About 19 patients did not show expansion but had the clinical symptoms of HD (group B). MtDNA deletions were classified into four groups according to size; 9 kb, 7.5 kb, 7 kb, and 5 kb. We found one of the four-mtDNA deletions in at least 90% of samples. Multiple deletions have also been observed in 63% of HD patients. None of the normal control (group C) showed mtDNA deletions. The sizes or locations of the deletions did not show a clear correlation with expanded CAG repeat and age in our samples. The study presented evidence that HD patients had higher frequencies of mtDNA deletions in lymphocytes in comparison to the controls. It is thus proposed that CAG repeats instability and mutant Htt are causative factor in mtDNA damage.     

A novel recombinant anti‐epidermal growth factor receptor peptide vaccine capable of active immunization and reduction of tumor volume in a mouse model

Over‐expression of epidermal growth factor receptor (EGFR) has been reported in a number of human malignancies. Strong expression of this receptor has been associated with poor survival in many such patients. Active immunizations that elicit antibodies of the desired type could be an appealing alternative to conventional passive immunization. In this regard, a novel recombinant peptide vaccine capable of prophylactic and therapeutic effects was constructed. A novel fusion recombinant peptide base vaccine consisting of L2 domain of murine extra‐cellular domain–EGFR and EGFR mimotope (EM‐L2) was constructed and its prophylactic and therapeutic effects in a Lewis lung carcinoma mouse (C57/BL6) model evaluated. Constructed recombinant peptide vaccine is capable of reacting with anti‐EGFR antibodies. Immunization of mice with EM‐L2 peptide resulted in antibody production against EM‐L2. The constructed recombinant peptide vaccine reduced tumor growth and increased the survival rate. Designing effective peptide vaccines could be an encouraging strategy in contemporary cancer immunotherapy. Investigating the efficacy of such cancer immunotherapy approaches may open exciting possibilities concerning hyperimmunization, leading to more promising effects on tumor regression and proliferation.

     

Radiation-induced breast angiosarcoma: report of two patients after accelerated partial breast irradiation (APBI) and review of the literature

BackgroundAngiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy.Case presentationwe introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient.DiscussionThe underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient’s specifications.ConclusionThere are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and survival.