In vitro study: green synthesis and evaluation of MgO/C-dots/DOX phosphorescent nanocomposites for photodynamic/photocatalytic therapy of tumors.

MgO nanoparticles (NPs) and carbon dots (C-dots) were synthesized by co-precipitation and hydrothermal techniques. In the next step, as-synthesized NPs were modified by C-dots. Then, polyethylene glycol (PEG) was conjugated with MgO/Cdots. Finally, Doxorubicin (Dox) as an anticancer drug was loaded on MgO/Cdots/PEG nanocomposites. The XRD pattern showed the characteristic peaks of C-dots and MgO. The FTIR spectrum showed that MgO/C-dots possessed the carboxyl functional groups, allowing DOX to be loaded onto MgO/C-dots/PEG through hydrogen bonds. The particle size of MgO, C-dots, MgO/C-dots, and MgO/C-dots/PEG/DOX was 20-30, 5-10, 30-40, and 100-130 nm, respectively, using TEM, DLS, and FESEM techniques. MgO, MgO/C-dots, and MgO/C-dots/DOX were fluorescent NPs when excited by a UV source. Anthracene and methylene blue were used as fluorescent probes to identify the reactive oxygen species (ROS) produced by UV excitation. The activity of MgO/C-dots and MgO/C-dots/DOX against colorectal cancer (C26) cells, after repeated 5-min illumination with both UV-light and red light LEDs, were measured by MTT assay. C26 cancer cells incubated with DOX-loaded MgO/C-dots and exposed to either wavelength (UV and red) killed ∼70% of cells. The green synthesized nanocomposites could act as anti-cancer photosensitizers probably by a photocatalytic mechanism.

TET2, DNMT3A, IDH1, and JAK2 Mutation in Myeloproliferative Neoplasms in southern Iran.

Background: Five epigenetic regulator mutations are considered in myeloproliferative neoplasms (MPN) that have prognostic and therapeutic values. Objective: We aimed to evaluate these mutations in MPNs among the Iranian population. Methods: We selected 5 mutations in 4 epigenetic regulatory genes [TET2, DNMT3A, IDH1 (rs147001633&rs121913499), and JAK2)] and evaluated 130 patients with MPNs including 78 Philadelphia chromosome negative (49 ETs, 20 PVs, and 9 PMFs) and 52 Philadelphia chromosome-positive patients as well as 51 healthy controls. Results: Eight patients (6.5%) carried the DNMT3A mutation, 35 (27%) were positive for TET2 mutation and 64 (49.3%) had the JAK2V617F mutation. In the healthy controls, 16 (31.4%) cases had the TET2 mutation (15 Heterozygote + 1 Homozygote) and one had heterozygote JAK2 mutation. There was no statistically significant difference between patient groups for any of these mutations, except for JAK2. The JAK2 mutation rate was 18 (90%), 25 (51%), 7 (77.8%), 14 (26.9%) in polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myelocytic leukemia, respectively. Patients aged 60 and older were more likely to carry the TET2 mutation (23% vs. 39% in younger and older than 60 years old individuals, p=0.025). IDH1 was not detected at all and PV had the highest TET2 mutation 7(35%). Two PMF patients had a history of bone marrow transplantation that were negative for IDH1and DNMT3A and one was positive for TET2 mutation. Conclusion: In the normal Iranian population, the heterozygote form of TET2 mutation is significant, especially in the elderly. No association was found between JAK2 and TET2 mutations. Both of them are more prevalent in the age group of 60 years and older. DNMT3A mutation has a low prevalence and occurs in both positive and negative MPNs.

Frequency of thyroid nodules in patients with ß-thalassemias in Southern Iran.

BACKGROUND: Although thyroid nodules are a common finding in the general population, determining the clinically important nodules is essential. We investigated thyroid nodules or cysts by thyroid ultrasonography (US) in patients with ß-thalassemia major (ß-TM) and intermedia (ß-TI). We also report a ß-TI patient who was diagnosed with thyroid cancer six months before our screening. METHODS: In this cross-sectional study, 178 patients with ß-thalassemias referred to the Thalassemia Clinic in a tertiary hospital affiliated to Shiraz University of Medical Sciences were investigated, from January to June 2016, by US. RESULTS: Thyroid nodules or cysts were detected in 11 patients [total: 6.17 %; 8 patients with ß-TM (8.2%) and 3 patients with ß-TI (3.7%)]. All nodules were < 1 cm in diameter and were not suspicious of malignancy. All patients, after 1 year of thyroid US follow-up, did not show any significant change in favor of malignancy. CONCLUSION: Based on our results, the frequency of thyroid nodules was similar to what was reported in the general population. However, a long-term follow-up of these patients is recommended because of the potential carcinogenic effects of iron and hepatitis C infection (HCV). To achieve more precise information, collaborative multicenter studies should be considered.

Combined X-ray radiotherapy and laser photothermal therapy of melanoma cancer cells using dual-sensitization of platinum nanoparticles.

Metal nanostructures are promising agents sensitizing by laser light and X-ray in photothermal therapy (PTT) and radiotherapy (RT) of cancer that improve treatment strategies of cancer. Nanoscale platinum materials are favorable in nanomedicine applications. In this study, platinum nanoparticles (PtNPs) were synthesized and applied for cancer therapy upon 808-nm laser light and X-ray radiation, or their combination. Two power densities of laser (1.0 and 1.5 W cm-2) and three X-ray doses (2, 4 and 6 Gy) were selected for irradiation of B16/F10 cell line at 24 and 72 h-post treatment. The synthesized PtNPs had a spherical shape with a diameter of 12.2 ± 0.7 nm, and were cytocompatible up to 250 µg mL-1. A photothermal conversion activity in a concentration-dependent manner at 72 h-post treatment was observed. Also, PtNPs represented cytotoxicity upon X-ray radiation doses of 2, 4, and 6 Gy after 24 h, while, 72-h time passing led to deeper outcomes. Dual radiation of laser light and X-ray into PtNPs considerably improved the treatment via reactive oxygen species (ROS) production. PtNPs can act as a novel dual absorber of laser light and X-ray, a common sensitizer, for treatment of cancer. The results of this study can be considered after further clinical investigations for treatment of tumor models.

An electrochemical signal-on apta-cyto-sensor for quantitation of circulating human MDA-MB-231 breast cancer cells by transduction of electro-deposited non-spherical nanoparticles of gold.

A highly simple, sensitive, specific and low-cost electrochemical apta-cyto-sensor for determination of circulating human MDA-MB-231 breast cancer cells was fabricated. Non-spherical nanoparticles of gold were electro-deposited in the presence of ethosuximide as a shape directing and size controlling agent. The nanoparticles had dimensions ranging 50-150 nm, and covered the underlying surface with a roughness factor of 8.03. The Non-spherical nanoparticles were then employed as the apta-cyto-sensor transducer. A 83-mer DNA aptamer that is specific to capturing the cell surface proteins was immobilized on the transducer surface, and binding with the cells was followed using the ferro/ferricyanide redox marker. The aptamer was immobilized within ∼200 min on the transducer surface. The cells were quantified with an equation of regression of ΔIp(µA) = (1.028 ±â€¯0.027) log (C (cell mL-1)) + (0.2199 ±â€¯0.0944), a sensitivity of 1.028 µA (log (concentration / cell mL-1))-1 and a quantitation limit of 2 cell mL-1, in a concentration range of 5 to 2 × 106 cell mL-1. The apta-cyto-sensor selectivity was also evaluated toward AsPC-1, Calu-6, HeLa, MCF-7 and melanoma B16/F10 cell lines. The apta-cyto-sensor had a fabrication reproducibility of 4.2%, regeneration capability of 5.1%, a stability of 35 days, and a potential application for the detection of MDA-MB-231 cells in the spiked blood serum samples with a sensitivity of 0.8975 µA (log (concentration / cell mL-1))-1 and a quantitation limit of 5 cell mL-1, in a concentration range of 10 to 1 × 103 cell mL-1. The apta-cyto-sensor would be applicable for breast cancer diagnosis at early stage.

Enhanced melanoma cell-killing by combined phototherapy/radiotherapy using a mesoporous platinum nanostructure.

BACKGROUND: Metal nanomaterials have a significant potential as photosensitizer and radiosensitizer. The purpose of this study was to evaluate the cytotoxicity of a platinum mesoporous nanostructure (Pt MN) toward a melanoma cancer cell line upon combined laser radiation (808 nm, 1 and 1.5 W cm-2) and X-ray irradiation (6 MV, 2, 4, and 6 Gy). METHODS: Pt MN was synthesized by a simple procedure and characterized by field emission scanning and transmission electron microscopy. A mouse malignant melanoma cell line C540 (B16/F10) was treated with Pt MN, laser light and/or X-ray. RESULTS: Pt MN had a mesoporous structure with a sponge-resemble shape comprised of ensembles of very small adhered particles of <11 nm and about 5-nm pores. While Pt MN represented a low toxicity toward and considerable uptake into the cell line in a concentration range of 10-100 µg mL-1, laser light radiation alone was also not toxic, and X-ray irradiation alone induced a limited toxicity, Pt MN was toxic against the cells in a dose dependent manner upon laser light radiation, X-ray irradiation, or their combined exposure. The killing efficacy of Pt MN upon X-ray irradiation was more obvious at 72 h post-treatment. The combined exposure (laser radiation followed by X-ray irradiation) led to a deep cell killing and a very low melanoma cell viability (∼1%). Significant melanoma cancer cell killing of Pt MN was due to reactive oxygen species (ROS) production upon combined exposure of laser and X-ray, while cell killing upon laser light radiation was due to heat generation. CONCLUSION: Pt MN was introduced as a supreme laser/X-ray sensitizer for treatment of cancer with a high ability to produce ROS and a potent impact on decreasing cell viability.

Association of IL-12 and TNF-α Polymorphisms with Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Cytokines are important factors determining the outcome of transplantation. The host ability in cytokine production may be affected by cytokine genes polymorphisms. OBJECTIVE: To investigate the effect of IL-12 and TNF-α gene polymorphisms on outcome of hematopoietic stem cell transplantation. METHODS: 90 bone marrow transplant recipients were included in this study. 30 (33%) of 90 recipients experienced graft-versus-host disease (GVHD). IL-12 and TNF-α gene polymorphisms were evaluated by PCR-RFLP and ARMS-PCR method, respectively. RESULTS: No significant difference in the distribution of IL-12 (rs3212227 +1188 A/C) and TNF-α (rs 1800629 -308 G/A) genotypes and alleles was observed between those with and without GVHD. There was no significant association between the distribution of genotypes and the recipient sex. CONCLUSION: IL-12 (rs3212227 +1188 A/C) and TNF-α (rs 1800629-308 G/A) genotypes and alleles were not risk factors for development of GVHD.

Evaluation of a self-nanoemulsifying docetaxel delivery system.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 µg mL-1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 µg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 µg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.

The protective effects of melatonin on blood cell counts of rectal cancer patients following radio-chemotherapy: a randomized controlled trial.

PURPOSE: We aimed to examine the radioprotective effects of melatonin on the blood cell counts of patients with rectum cancer undergoing radiotherapy. MATERIALS AND METHODS: This double-blind placebo-controlled study was conducted on 60 rectal cancer patients who were referred to Rajaii Hospital of Babolsar, Iran. An equal number of patients were randomly assigned to the control group which received placebo and study group which received 20 mg melatonin a day as an intervention. The melatonin was administered 5 days a week for 28 days. Blood samples were taken before melatonin received on day 1 and also day 28; then, to measure the changes in blood cell counts representing our primary outcomes, the samples were analyzed by Sysmex K810i auto-analyzer. RESULTS: Our results showed that the platelet, white blood cells, lymphocyte, and neutrophil population reduction induced by radiotherapy were slighter or even insignificant in melatonin recipients compared to control. However, the difference between red blood cells in both groups was not significant. CONCLUSION: Our results are indicating that melatonin could prevent or minimize the unfavorable effects of radiotherapy on blood cell count reductions by attenuating the adverse influence of radiation, probably through stimulation of cellular antioxidant potential as previously reported in animal models. IRANIAN REGISTRY OF CLINICAL TRIALS (IRCT): Registry No. IRCT2016021626586N1.

Blood Product Transfusion in Liver Transplantation and its Impact on Short-term Survival.

BACKGROUND: Estimation of the amount of blood products required during liver transplantation can help provision of adequate blood supply, minimize transfusion-associated complications, and plan for preventive measures in high risk patients. OBJECTIVE: To investigate independent predictors of peri-operative blood product transfusion and its impact on short-term survival of liver transplant recipients. METHODS: In a cross-sectional study, old charts of patients who underwent liver transplantation between March 2003 and March 2013 at Namazi Hospital, Shiraz, Iran, were reviewed. The mean amount of blood product utilized during surgery and hospital stay and the related factors, including demographic characteristics, pre-transplant laboratory data, pre-transplant clinical data, operation data, and post-transplantation data were recorded. RESULTS: We studied 1198 patients who underwent liver transplantation. The mean±SD amounts of red blood cells, fresh frozen plasma, and platelet transfusion during surgery and hospital stay were 2.67±3.5, 2.06±3.8, and 1.6±3.8 units, respectively. The mortality rate was significantly higher in patients who received high amounts of blood products (p<0.001). The mean amount of blood products' utilized during operation was significantly (p<0.001) decreased from 2003 to 2013.The mean amount of packed cell usage during operation and hospital stay was significantly (p<0.001) correlated with age, technique of surgery, serum albumin level, cirrhosis, blood urea nitrogen, length of operation, and prothrombin time. CONCLUSION: Pre-operative factors may predict blood transfusion requirements in patients undergoing liver transplantation. Therefore, evaluation of patients before operation should be considered to provide adequate blood supply and minimize transfusion-associated complications. Understanding pre-operative factors associated with rate of transfusion may help us to best utilize the limited available blood resources.

Intrathecal Autologous Bone Marrow-Derived Hematopoietic Stem Cell Therapy in Neurological Diseases.

BACKGROUND: Cellular transplantation is a promising treatment strategy for neurological diseases. OBJECTIVE: To report the results of intrathecal hematopoietic stem cell therapy in different neurological diseases in the past 6 years in a single center. METHODS: From October 2011 to September 2018, 220 patients with various neurological diseases were transplanted intrathecally by their bone marrow stem cells. To have a longer follow up, we only reported the first 80 patients, transplanted up to July 2015-10 patients had spinal cord injuries and paralysis, 12 had advanced Parkinson's disease, 28 had cerebral palsy, 7 had hypoxic brain damage, 2 had autism, 4 had multiple sclerosis, 5 had progressive cerebellar atrophy, and 12 had other neurological diseases. The patients were admitted to the Bone Marrow Transplant Unit. On the first day, 50-200 (median 100) mL bone marrow was aspirated from the patients' posterior iliac crests, mixed with 120 mL culture media (RPMI), and 12 mL heparin. The samples were then transferred to immunology lab in cold box. Mononuclear cells (MNCs) were separated by a Ficoll-Hypaque gradient, washed, and suspended in ringers. Cell viability was assessed with trypan blue viability test. Transplantation was performed 3-4 hours after bone marrow collection. 5-10 mL of the cerebrospinal fluids were aspirated and about 20 mL MNCs (containing stem cells) in ringers were injected intrathecally (IT). The patients were laid down on their back for 4-5 hours. The median number of MNCs was 4×107 (range 1-450×107). The median viability of the cells was 90% (range 60%-98%). The patients received intravenous ceftriaxone every 12 hours and were discharged from the hospital few days after autologous stem cell therapy. RESULTS: We noted clinical improvements in 9 of 12 patients with Parkinson's disease, 20 of 28 patients with cerebral palsy, 6 of 7 patients with hypoxic brain damage, 2 of 4 patients with multiple sclerosis, and 4 of 5 patients with cerebellar atrophy. The improvements were noted after 2-4 weeks of cell therapy. There were no improvements in patients with spinal cord injury and complete paralysis and those with autism. There were variable improvements in other patients treated. CONCLUSION: Most patients with advanced Parkinson's disease, cerebral palsy, hypoxic brain damage, progressive cerebellar atrophy, and kernicterus neuropathy reported clinical effects of this safe intervention resulting in better functioning and an increased quality of life.

Association between IRF1 Gene Expression and Liver Enzymes in HBV-infected Liver Transplant Recipients with and without Experience of Rejection.

BACKGROUND: Liver function indices and anti-viral immune regulatory markers can both improve graft outcomes, which lead to better post-transplantation management and increase the possibility of surveillance in liver transplant recipients with chronic hepatitis B virus (HBV) infection. OBJECTIVE: To determine the association between the interferon regulatory factor 1 (IRF1) mRNA levels and liver enzymes in HBV-infected liver transplant recipients with and without experience of rejection. METHODS: A total of 46 chronic HBV-infected patients who had undergone liver transplant surgery was divided into 2 groups of recipients "with rejection" and "without rejection.". Blood samples were collected form each patient on days 1, 4, and 7 post-transplantation. A SYBER GREEN real-time PCR was used to evaluate the expression level of IRF1 in liver recipients. Liver enzyme activities were also measured in all patients. RESULTS: The expression of IRF1 in the patients with rejection was up-regulated at all 3 follow-up days compared with those without rejection. The serum levels of ALT and AST were more than normal levels at 3 follow-up times in both study groups. Significant differences were found in IRF1 gene expression levels and also serum ALT levels between those with and without rejection after 7 days post-transplantation. CONCLUSION: The IRF1 expression and serum ALT levels were increased significantly in patient with rejection compared to those without rejection. IRF1, an inflammatory factor, may also intensify induction of inflammatory pathways in engrafted liver and promote liver inflammation and injuries leading to liver enzymes elevation in patients with graft rejection.

A large case series on surgical outcomes in congenital factor XIII deficiency patients in Iran.

Essentials Data on surgery in factor XIII (FXIII) deficiency patients are scarce and lack standardized guidelines. Variable dosage of 10-50 U kg-1 was given to FXIII deficiency patients undergoing surgery. Surgical outcomes showed excellent hemostasis with a minimal risk of post-operative complications. Surgery can be performed safely in FXIII deficiency patients following FXIII administration. SUMMARY: Background The lack of accepted standardized surgical guidelines leads to dependence on the treating physicians' and centers' experiences. Aim Our aim is to evaluate the surgical outcomes of a large group of congenital factor XIII deficiency (FXIIID) patients. Methods A case series study was conducted prior to surgery on congenital FXIIID patients in two major referral centers located in Iran from 2010 to 2016. All patients were on prophylaxis using plasma factor XIII concentrate (10 U kg-1 , every 28 days) except for three patients. Single doses of 10 U kg-1 or 30 U kg-1 plasma factor XIII concentrate were given before a minor procedure and circumcision, respectively. Two doses of plasma factor XIII concentrate, one 30 U kg-1 prior to the procedure and the second dose of 30 U kg-1 on postoperative day 3, were given for major surgery. The dose was 50 U kg-1 both before and after neurosurgical procedures. Results One hundred and sixty-two FXIIID patients underwent minor, major and obstetrical/gynecological surgeries. Median age of the patients was 14 years (ages ranged 15 days to 47 years). The male-to-female ratio was 89/73. Five postoperative complications, two bleeding and three thrombosis, were recorded. Conclusion Our study showed excellent hemostasis in FXIIID patients undergoing surgeries. During the period of these surgeries, we observed only 1.8% postoperative complications. Surgery can be performed safely in FXIIID patients, and our proposed treatment regimens lead to adequate hemostatic coverage with minimal risk, for both minor and major surgeries.

A national survey of natural radionuclides in soils and terrestrial radiation exposure in Iran.

In the past, some efforts have been made for measuring natural radioactivity and evaluating public exposure to natural radiation in certain areas of Iran especially in well-known High Level Natural Radiation Areas (HLNRA) in Ramsar and Mahallat. However, the information on radionuclide concentrations, and, consequently, terrestrial radiation exposure for many other areas are not available. There was therefore a need for a systematic and nation-wide survey. For this purpose, 979 soil samples from 31 provinces were collected. The activity concentrations of 40K, 226Ra and 232Th were measured by HPGe detector. The average activity concentrations for Iran were found to be 457.7 Bq/kg for 40K, 24.3 Bq/kg for 226Ra and 25.8 Bq/kg for 232Th. Results were compared with previous regional or provincial surveys. The population-weighted average outdoor and indoor annual effective dose due to external exposure to terrestrial sources of radiation are 0.06 mSv and 0.33 mSv, respectively. It was shown that there is a significant correlation between the activity concentrations of 232Th and 40K in soil. In addition, the results of chi square tests show normal and lognormal distributions cannot be considered for the frequency distributions of activity concentration of 232Th and 226 Ra while 40K has a normal distribution.

In vitro proliferation and differentiation of human bone marrow mesenchymal stem cells into osteoblasts on nanocomposite scaffolds based on bioactive glass (64SiO2-31CaO-5P2O5)-poly-l-lactic acid nanofibers fabricated by electrospinning method.

Electrospinning method was employed for fabrication of SiO2-CaO-P2O5 bioactive glass (BG) nanofibers, poly-l-lactic acid (PLLA) nanofibers and nanocomposite scaffolds fabricated from as-prepared nanofibers. Characterization of the prepared nanofibers and scaffolds by XRD, FTIR, and SEM techniques revealed the formation of nanofibers with mean diameter of about 500nm and fully fibrous scaffolds with porous structure and interconnected pores. The growth, viability and proliferation of cultured human bone marrow mesenchymal stem cells in the fabricated nanofibers and bioactive glass-poly-l-lactic acid (BG-PLLA) nanocomposite scaffolds were studied using various biological assays including MTT, ALP activity, calcium deposit content, Alizarin red staining, and RT-PCR test. Based on the obtained results, incorporation of BG nanofibers in the nanocomposite scaffolds causes the better biological behavior of the scaffolds. In addition, three-dimensional and fibrous-porous structure of the scaffolds further contributes to their improved cell behavior compared to the components.

The Immunomodulatory Effect of Bone-Marrow Mesenchymal Stem Cells on Expression of TLR3 and TLR9 in Mice Dendritic Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory effect on immune cells including dendritic cells (DCs). DCs are the most potent antigen-presenting cells (APC). MSCs have been found to modulate both differentiation and function of DCs. DCs express a broad range of Toll-like receptors (TLR), which play a critical role in DCs maturation and function. OBJECTIVE: To evaluate expression level of TLR3 and TLR9 transcripts in DCs following treatment with MSCs supernatant. METHODS: MSCs and DCs were derived from adult BALB/c mice bone marrow and spleen, respectively. MSCs supernatant was harvested following 24, 48, and 72 hours. Isolated DCs were treated with MSCs supernatant and incubated for 24 and 48 hours. TLR3 and TLR9 transcript levels were evaluated using real-time PCR. RESULTS: The results showed that 48 and 72 hours MSCs supernatant significantly decreased the expression of TLR3 in DCs following 24 and 48 hours incubation in comparison with untreated cells (p<0.01). Moreover, 48 hours of treatment with 24, 48 and 72 hours MSCs supernatant significantly decreased TLR9 transcript level (p<0.05). CONCLUSION: TLR3 and TLR9 mRNA expression decreases in DCs after incubation with MSCs culture supernatant. This confirms the immunomodulatory role of MSCs in cell-base therapy.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human breast milk and associated health risks to nursing infants in Northern Tanzania.

This is the first study to report organochlorines (OCs), including chlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human milk from Tanzania. The main aims of this study were to assess the level of contamination and the possible health risks related to OC exposure in nursing infants from the Northern parts of Tanzania. Ninety-five healthy mother-infant couples attending Mount Meru Regional Referral Hospital (MMRRH), Arusha, Tanzania, were assessed for associations between maternal/infant characteristics, i.e. mother's age, BMI, gestational weight gain, occupation, residence and fetal growth parameters and breast milk levels of OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dieldrin and PCBs. p,p'-DDE and p,p'-DDT were detected in 100% and 75% of the breast milk samples, respectively, and ranged between 24 and 2400ng/g lipid weight (lw) and

Association of GSTO2 (N142D) Genetic Polymorphism and Acute Rejection of Liver.

BACKGROUND: Acute rejection is the main problem in liver transplantation that occurs in the first days or months of transplantation. It includes histological and cellular rejection. Acute histological rejection is confirmed by biopsy. Glutathione S-transferase family is the most important genes in phase II detoxification working in xenobiotic and drug metabolism. GSTO2 is one of the members of this family. GSTO2 (N142D) polymorphism may influence metabolism of immunosuppressive drugs. OBJECTIVE: To determine if GSTO2 polymorphism has association with acute liver rejection. METHODS: The present study included 120 patients with histological-proven acute liver rejection and 182 patients without acute rejection. Both groups were matched for sex and age. To determine variants of GSTO2, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was a significant association between the GSTO2 genotype and acute liver rejection (NN: OR: 3.642, 95% CI: 1.179-5.444) and (ND: OR: 2.533, 95% CI: 1.672-8.149) compared to those with DD geneotype. CONCLUSION: Recipients with either NN or ND genotype for GSTO2 are more likely to develop acute liver rejection compared to those with DD genotype.

Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma.

The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and is a key regulator of the aberrant transcriptome characteristic of this disease. Here we show that IRF5 upregulation in HL is driven by transcriptional activation of a normally dormant endogenous retroviral LOR1a long terminal repeat (LTR) upstream of IRF5. Specifically, through screening of RNA-sequencing libraries, we detected LTR-IRF5 chimeric transcripts in multiple HL cell lines but not in normal B-cell controls. In HL, the LTR was in an open and hypomethylated epigenetic state, and we further show the LTR is the site of transcriptional initiation. Among HL cell lines, usage of the LTR promoter strongly correlates with overall levels of IRF5 mRNA and protein, indicating that LTR transcriptional awakening is a major contributor to IRF5 upregulation in HL. Taken together, oncogenic IRF5 overexpression in HL is the result of a specific LTR transcriptional activation. We propose that such LTR derepression is a distinct mechanism of oncogene activation ('onco-exaptation'), and that such a mechanism warrants further investigation in molecular and cancer research.