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BackgroundAlloantibody production is one of the most challenging complications in transfusion‐dependent thalassaemia patients. Haemolytic anaemia, an increase in blood consumption, difficulty in haematopoietic stem cell transplantation and reduced quality of life are consequences of alloimmunisation. The most predisposed antigens (Ags) for alloantibody development are Rh and Kell blood group Ags.ObjectiveThe aim of the present study is to evaluate any correlation between HLA‐DRB1 alleles and Rh and Kell alloantibodies.Materials and MethodsFifty‐two non‐responders (control) and 54 responders (case) were enrolled in this study. Alloantibody detection was performed using the tube method. Genotyping of HLA‐DRB1*01 and HLA‐DRB1*15 was conducted by single‐specific primer‐polymerase chain reaction.ResultsIn the responder group, 77.8% were hyper‐responders (more than one alloantibody), and only 22.2% were mono‐responders. Most detected alloantibodies were Anti‐K (94.4%), followed by Anti‐E (64.8%), Anti‐C (29.6%) and Anti‐D (25.9%). There was a significant difference in HLA‐DRB1*15 between responder and non‐responder groups, 73.7% vs 26.3%, respectively. (P = .029, OR = 3.290; 95%CI). Our results showed that HLA‐DRB1*15 was more frequent in hyper‐responders than mono‐responders (92.9% vs 7.1%) (P = .007). The greatest HLA‐DRB1*15 was seen in Anti‐K (P = .014, odds ratio [OR = 3.784]; 95% confidence interval [CI]) and Anti‐E (P = .011, OR = 3.609; 95%CI) alloantibodies. There is no association between HLA‐DRB1*01 and alloimmunisation.ConclusionOur findings showed that there is a significant correlation between HLA‐DRB1*15 and Anti‐K and Anti‐E alloantibodies. These findings can be useful in detecting susceptible thalassaemic patients and improving transfusion management.

Pancreatic and duodenal homeobox 1 (Pdx1) and Sonic hedgehog (Shh) are the key regulators of beta‐cell function. In vitro experiments have shown that there is significant cooperation between Pdx1 and Shh with regard to the production and maintenance of insulin‐producing cells ( IPC s). In this study, the combined effect of Pdx1 overexpression and Shh manipulation on the function of adipose tissue‐derived IPC s was determined. A eukaryotic expression vector ( Pdx1‐ pCDNA 3.1(+)) was constructed and transfected into a Chinese hamster ovary ( CHO ) cell line. Adipose tissue‐derived mesenchymal stem cells ( ADMSC s) obtained from rats were assigned to two groups [control (C) and manipulated (M)] and differentiated into IPC s. Manipulated cells were treated with a mixture of FGF ‐β and cyclopamine and recombinant Shh protein at days 3 and 11, respectively, and transfected with Pdx1‐ pCDNA 3.1(+) at day 10. The expression of multiple genes related to function of beta cells was analyzed using real‐time PCR . The functionality of IPC s in vitro was analyzed through dithizone ( DTZ ) staining and ELISA . IPC s were injected into the tail vein of diabetic rats, and blood glucose and insulin concentrations were measured. CHO cells transfected with Pdx1‐ pCDNA 3.1(+) showed a significantly higher expression of Pdx1 compared with nontransfected cells. Manipulated IPC s exhibited a significantly higher expression of MafA, Nkx2.2, Nkx6.1, Ngn3, insulin , and Isl1 and a higher insulin secretion in response to glucose challenge in relation to control cells. Rats that received manipulated IPC s exhibited a higher ability to normalize blood glucose and insulin secretion when compared to controls. Our protocol might be used for more efficient cell therapy of patients with diabetes in the future.

Background: Because IL2RA is considered a predisposing factor in the incidence of both type I diabetes and multiple sclerosis (MS), and considering that both are autoimmune diseases, some studies suggest a correlation between type I diabetes and MS. Objectives: The aim of this study was to examine the prevalence of type I diabetes among people with MS. Patients and Methods: The study subjects comprised 100 patients with MS from the Khuzestan multiple sclerosis center at rehabilitation school of Jundishapur University of Medical Sciences, whose diagnosis of MS had been confirmed by a specialist, and were not being treated with steroids. Subjects were selected from patients younger than 30 years old. After filling out an application form, 5 mL fasting venous blood and 5 mL after 2 hours were taken. The blood glucose level was measured with a kit (Zist Shimi) using the enzymatic method. Results: The mean age of the participants was 24.28 years. The rate of type I diabetes was equal to 4% of the total sample, while 18% of all patients had impaired fasting glucose. Conclusions: Given the high level of impaired fasting glucose among patients in this study, it is likely that MS provides the basis for the incidence of glucose metabolism disorders. To prove this, further studies with larger sample sizes are required.

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Background: Previous studies reported the inevitable destructive effects of radiotherapy on normal adjacent cells. Ascorbic Acid (AA) has been proposed as an effective anti-cancer agent with no obvious effect on normal cells. Objective: We studied the effects of Ascorbic acid in combination with radiotherapy on human pancreatic carcinoma cell line. Methods: The human pancreatic cancer cells were cultured and divided into four groups: control group (A) without any treatment, group B that received 2Gy radiotherapy alone, group C that was treated with 4mM AA alone and group D that was co-treated with AA and radiotherapy. Cell viability, DNA fragmentation, expression of apoptotic genes and Reactive oxygen species (ROS) production were determined in treated cells. Results: There was a noticeable decrease in cell viability after treatment with AA (and/or) radiotherapy. All treated groups showed elevated ROS production, Bax/Bcl2 expression, DNA fragmentation and cytotoxycity compared with control group. Cells under combination therapy showed the most cytotoxicity. Conclusion: Our results suggest that AA at dose of 4 mM may be used as an effective radio-sensitizing agent in pancreatic cancer cell line.

Background: Some studies have shown anticarcinogenic effects of high dose L-Ascorbic Acid. However, there are controversies around the therapeutic administration of Ascorbic acid as an anticancer medicine. Objective: we conducted a case-control study to investigate the role of pharmacologic concentration of Ascorbic acid on viability and angiogenesis of human colon cancer (HT29) cell line. Methods: The HT29 cells were cultured in DMEM-HG and treated with 10 mM ascorbic acid for 3h. The culture medium was exchanged, and after incubation at 37 ˚C for 24 h, the cells were collected and utilized to evaluate viability, ROS production, gene expression and protein expression levels. The control group consisted of untreated HT29 cells. The viability of the cells was determined using the MTT method. Moreover, Nitro Blue Tetrazolium (NBT) was used to detect the ROS production capacity. The mRNA transcript’s level and protein expression were evaluated by Real-time PCR and Western blotting, respectively. Results: The ascorbic acid-treated group showed a significant increase in ROS production and an obvious reduction in viability compared to the control group. The treated group showed significant increased levels of both early apoptotic markers (Bax, Cyt C, Caspase3, and Caspase 9) and late apoptotic marker (Caspase 8). Bcl2 expression showed significantly decreased levels relative to the control group. Ascorbic acid therapy substantially reduced the expression of bFGF, bFGFR, PDGF, PDGFR and PLC- γ compared to the control group. Conclusion: The results confirm that high- dose L-ascorbic acid reduces HT29 cell line viability in vitro.

Background and Objectives: Combination therapy improves the effect of chemotherapy on tumor cells. Magnolol, used in treating gastrointestinal disorders, has been shown to have anti-cancer properties. We investigated the synergistic effect of cisplatin and magnolol on the viability and maintenance of MKN-45 gastric cancer cells. Materials and Methods: The toxicity of magnolol and/or cisplatin was determined using the MTT technique. The trypan blue method was used to test magnolol and/or cisplatin’s effect on MKN-45 cell growth. Crystal violet staining was used to assess the treated cells’ tendency for colony formation. The expression of genes linked to apoptosis, cell cycle arrest, and cell migration was examined using the qPCR method. Results: According to MTT data, using magnolol and/or cisplatin significantly reduced cell viability. The ability of the treated cells to proliferate and form colonies was also reduced considerably. Magnolol and/or cisplatin treatment resulted in a considerable elevation in Bax expression. However, the level of Bcl2 expression was dramatically reduced. p21 and p53 expression levels were significantly increased in the treated cells, while MMP-9 expression was significantly reduced. Conclusions: These findings show that magnolol has a remarkable anti-tumor effect on MKN-45 cells. In combination with cisplatin, magnolol may be utilized to overcome cisplatin resistance in gastric cancer cells.