Complications in patients with transfusion dependent thalassemia: A descriptive cross-sectional study.

Background and Aims: One of the most common hemoglobinopathies globally related to blood transfusion and iron overload in the body is thalassemia syndrome. Increasing ferritin levels can cause severe damage to the patient's body organs. This study aims to evaluate the complications of iron overload on vital body organs in patients with transfusion-dependent beta-thalassemia. Methods: This descriptive cross-sectional study was performed in Iran University of Medical Sciences Hospitals on patients with a beta-thalassemia major with frequent blood transfusions. To evaluate the effect of iron overload on vital body organs, hematologic and blood analysis, echocardiography with measurement of pulmonary artery pressure (PAP) and ejection fraction (EF) tests, bone densitometry, and audiometric tests were performed for all patients. Results: Of the 1010 patients participating in this study, 497 (49%) were males, 513 were (51%) females aged 5-74 years, and the majority of participants (85%) were over 20 years old. This study demonstrated that increasing ferritin levels had no notable correlation with sex, cholesterol, low-density lipoprotein, parathyroid hormone, T4, and aspartate aminotransferase. However, elevating ferritin levels had significant correlations with increasing triglyceride, phosphorus, thyroid stimulating hormone, alkaline phosphatase, alanine transaminase, and PAP levels, age, hearing disorders, splenectomy, osteoporosis, and decreasing high-density lipoprotein, body mass index, calcium, and EF levels. Conclusion: Improvement in beta-thalassemia patients' survival and quality of life can be due to multidisciplinary care in a comprehensive unit through regular follow-up and early complication detection.

Angiogenesis, coagulation, and fibrinolytic markers in acute promyelocytic leukemia (NB4): An evaluation of melatonin effects.

Melatonin is a powerful biological agent that has been shown to inhibit angiogenesis and also exerts anti-inflammatory effects. It is well known that new blood vessel formation (angiogenesis) has become an urgent issue in leukemia as well as solid tumors. Acute promyelocytic leukemia (APL) is a form of liquid cancer that manifests increased angiogenesis in the bone marrow of patients. Despite high-rate curable treatment with all-trans-retinoic acid (ATRA) and recently arsenic-trioxide (ATO), early death because of hemorrhage, coagulopathy, and Disseminated intravascular coagulation (DIC) remains still a concerning issue in these patients. It is, therefore, urgent to seek treatment strategies with antiangiogenic capabilities that also diminish coagulopathy and hyperfibrinolysis in APL patients. In this study, a coculture system with human umbilical vein endothelial cells (HUVECs) and NB4 APL cells was used to investigate the direct effect of melatonin on angiogenesis and its possible action on tissue factor (TF) and tissue-type plasminogen activator-1 (TPA-1) expression. Our experiments revealed that HUVEC-induced angiogenesis by cocultured NB4 cells was suppressed when melatonin alone or in combination with ATRA was added to the incubation medium. Melatonin at concentrations of 1 mM inhibited tube formation of HUVECs and also decreased interleukin-6 secretion and VEGF mRNA expression in HUVEC and NB4 cells. Taken together, the results of this study demonstrate that melatonin inhibits accelerated angiogenesis of HUVECs and ameliorates the coagulation and fibrinolysis indices stimulated by coculturing with NB4 cells.

Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research.

BACKGROUND: Breast cancer is one of the most common malignancies in women, with one in 20 globally. Oncolytic viruses have recently been the first step in the biological treatment of cancer, either genetically engineered or naturally occurring. They increase specifically inside cancer cells and destroy them without damaging normal tissues or producing a host immune response against tumour cells or expressing transgenes. One of the most known members of this family is the Newcastle disease virus (NDV), a natural oncolytic virus that selectively induces apoptosis and DNA fragmentation in human cancer cells. METHODS: This study performed biochemical and molecular investigations with variable doses of NDV (32, 64, 128 HAU) and liposomal doxorubicin (9 mg/kg) on mouse triple-negative mammary carcinoma cell line 4T1 and BALB/c models tumours for the first time. RESULTS: Real-time quantitative PCR analysis in NDV-treated animal tumours showed increased expression of P21, P27 and P53 genes and decreased expression of CD34, integrin Alpha 5, VEGF and VEGF-R genes. Additional assessments in treated mouse models also showed that NDV increased ROS production, induced apoptosis, reduced tumour size and significantly improved prognosis, with no adverse effect on normal tissues. CONCLUSIONS: These findings all together might indicate that NDV in combination with chemotherapy drugs could improve prognosis in cancer patients although many more conditions should be considered.

Role of curcumin on miR-26a and its effect on DNMT1, DNMT3b, and MEG3 expression in A549 lung cancer cell.

CONTEXT: Most of the patients diagnosed with non-small cell lung cancer (NSCLC) are in their advanced stages and as a result might not be cured in spite of the advances in aimed therapy. In the recent years, the role of noncoding RNAs (ncRNAs) has been expanded to cancer as potential targets for RNA-based epigenetic therapies. Curcumin, as an active ingredient, is associated with epigenetic alterations, and it might modulate the expression of tumor suppressor and oncogenic microRNAs. MATERIALS AND METHODS: In this study, we investigated the RNA-based epigenetic effects of curcumin on NSCLC, and the effect of curcumin on A549 cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The expression of miR-26a, MEG3, DNA methyltransferase 1 (DNMT1), and DNMT3 beta (DNMT3b) was assessed by quantitative polymerase chain reaction. STATISTICAL ANALYSIS USED: Data analysis was done using Prism®6 software (GraphPad Software, Inc., La Jolla, CA, USA), and statistical analysis was performed using t-test between control and vitality samples. RESULTS: The results showed a significant increase (P < 0.05) of miR-26a expression which in turn was associated with a significant decrease (P < 0.05) in expression of DNMTs and subsequently a significant increase in MEG3 expression (P < 0.05) in A549 cell line after adding curcumin in the media. CONCLUSION: Considering all the data together, we could speculate the role of curcumin in ceasing the progression of cancer in its early stages and might be considered a potential drug for the treatment of NSCLC-derived lung cancer by establishing a meaningful relationship between epigenetic mechanisms and ncRNAs.

Plasma miR-183-5p in colorectal cancer patients as potential predictive lymph node metastasis marker.

Background: Lymph node metastasis (LNM) is a point that often, treatment is not effective in colorectal cancer (CRC). Clinical and pathologic markers of prognosis help clinicians in selecting patients for adjuvant therapy after surgical resection in CRC. MiR-183-5p has been demonstrated to play as an oncogene in CRC, although its biological role still remains unclear. The aim of this study was to evaluate the expression of miR-183-5p in CRC and its potential relevance to clinicopathological characteristics as a prognostic biomarker. Materials and Methods: In this case-control study, 33 CRC plasma samples at stage I-II-III, as well as plasma samples from 13 healthy controls, were collected. The relative expression levels of miR-183-5p in cancer and the normal samples were measured by quantitative real-time PCR. We analyzed their correlation with clinicopathological parameters and prognostic value. Results: Our results indicated that miR-183-5p was significantly overexpressed in CRC samples compared to healthy controls (P < 0.001) from a cutoff value of 3.9 with a sensitivity of 89% and a specificity of 91% and an AUC value of 0.74. Further analysis showed that a high plasma expression level of miR-183-5p was significantly associated with LNM and higher tumor/node/metastases stage (III) (P-value < 0.001).In conclusion, the overexpression of miR-183-5p is highly related to advanced clinical stage, LNM and poor prognosis of CRC, indicating that miR-183-5p may serve as a predictive biomarker for the prognosis or the aggressiveness of CRC.

Evaluation of circulating miR-21 and miR-222 as diagnostic biomarkers for gastric cancer.

INTRODUCTION: Gastric cancer is responsible for a large number of death worldwide and its high death rate is associated with a lack of noninvasive tools in GC diagnosis. MicroRNAs (miRNAs), as gene regulators, were shown to dysregulate in different types of cancer. Moreover, it is proven that miRNAs are stable in serum/plasma, so they can be used as a potential noninvasive marker in GC diagnosis. The objective of this study is to investigate the plasma miRNA expression in GC samples compared to controls as a potential biomarker in cancer diagnosis. MATERIALS AND METHODS: Expression levels of miR-21 and miR-222 were assessed using quantitative real-time polymerase chain reaction in plasma of 30 GC patients and 30 healthy controls. Diagnostic value of selected miRNAs was evaluated using receiver operating characteristic curve. Target prediction was done using bioinformatics tools to investigate the signaling pathways and function of the selected miRNAs. RESULTS: Our results demonstrated that the expression levels of miR-21 and miR-222 were significantly higher in GC plasma than in the controls (P < 0.0001, P = 0.043). The sensitivity and specificity for miR-21 and in plasma were 86.7% and 72.2% and for miR-222 were 62.5% and 56.2%, respectively. Bioinformatics analysis revealed that most target genes of miR-21 and miR-222 are involved in cancer-related signaling pathway such as tumor initiation and progression. CONCLUSION: Our results indicated that miR-21 and miR-222 in plasma samples can be served as a potential noninvasive tool in GC detection. Furthermore, the miRNA target prediction manifested that miR-21 and miR-222 involve in key processes associated with GC initiation and development.

Nanocomposite scaffold seeded with mesenchymal stem cells for bone repair.

The mechanical property of bone tissue scaffolds is one of the most important aspects in bone tissue engineering that has remained problematic. In our previous study, we fabricated a three-dimensional scaffold from nano-hydroxyapatite/gelatin (nHA/Gel) and investigated its efficiency in promoting bone regeneration both in vitro and in vivo. In the present study, the effect of adding silicon carbide (SiC) on the mechanical and biological behaviors of the nHA/Gel/SiC and bone regeneration in vivo were determined. nHA and SiC were synthesized and characterized by the X-ray diffraction pattern and transmission electron microscope image. Layer solvent casting, freeze drying, and lamination techniques were applied to prepare these scaffolds. Then, the biocompatibility and cell adhesion behavior of the synthesized nHA/Gel/SiC scaffolds were investigated. For in vivo studies, rats were categorized into three groups: blank defect, blank scaffold, and rat bone marrow mesenchymal stem cells (rBM-MSCs)/scaffold. After 1, 4, and 12 weeks post-injury, the rats were sacrificed and the calvaria were harvested. Sections with a thickness of 5 µm thickness were prepared and stained with hematoxylin-eosin and Masson's Trichrome, and immunohistochemistry was performed. Our results showed that SiC effectively increased the mechanical properties of the nHA/Gel/SiC scaffold. No significant differences were observed in biocompatibility, cell adhesion, and cytotoxicity of the nHA/Gel/SiC in comparison with the nHA/Gel nanocomposite. Based on histological and immunohistochemical studies, both osteogenesis and collagenization were significantly higher in the rBM-MSCs/scaffold group, quantitatively and qualitatively. The present study strongly suggests the potential of SiC as an alternative strategy to improve the mechanical and biological properties of bone tissue engineering scaffolds, and shows that the pre-seeded nHA/Gel/SiC scaffold with rBM-MSCs improves osteogenesis in the engineered bone implant.

In vitro activity of probiotic Lactobacillus reuteri against gastric cancer progression by downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor gene expression.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death, and most patients represent metastatic phenotype at the time of diagnosis. Urokinase plasminogen activator (uPA) system is well known for its critical roles in cancer cells invasion since uPA/uPA receptor (uPAR) overexpresses in several cancers. Subsequently, suppression of uPA/uPAR gene expression improves patients overall survival and prevents cancer progression. OBJECTIVES: The aim of the current study was to investigate possible effects of live Lactobacillus reuteri as a probiotic in inhibition of GC cells proliferation and invasion. MATERIALS AND METHODS: Human gastric adenocarcinoma epithelial cell line (AGS) cells were treated with different ratios of live L. reuteri and were incubated for 24, 48, and 72 h. Viability of cancer cells was measured with 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay, and the effects of L. reuteri on uPA/uPAR gene expression were assessed by real-time polymerase chain reaction. RESULTS: Our results showed that L. reuteri inhibits cell proliferation significantly in dose-dependent manner. Expressions of uPA and uPAR were downregulated followed by co-incubation of AGS cells and live L. reuteri compared to untreated-based line level. CONCLUSION: This study provides strong support in the role of L. reuteri in suppression of GC cell invasion by downregulation of pathways which is involved in extracellular matrix degradation such as uPA and uPAR.