Vitamin C promotes pluripotency of human induced pluripotent stem cells via the histone demethylase JARID1A

Somatic cells can be reprogramed into induced pluripotent stem (iPS) cells by defined factors, which provide a powerful basis for personalized stem-cell based therapies. However, cellular reprograming is an inefficient and metabolically demanding process commonly associated with obstacles that hamper further use of this technology. Spontaneous differentiation of iPS cells cultures represents a significant hurdle that hinder obtaining high quality iPS cells for further downstream experimentation. In this study, we found that a natural compound, vitamin C, augmented pluripotency in iPS cells and reduced unwanted spontaneous differentiation during iPS cells maintenance. Gene expression analysis showed that vitamin C increased the expression of the histone demethylase JARID1A. Furthermore, through gain- and loss-of-function approaches, we show that JARID1A is a key effector in promoting pluripotency and reducing differentiation downstream of vitamin C. Our results therefore highlight a straightforward method for improving the pluripotency and quality of iPS cells; it also shows a possible role for H3K4me2/3 in cell fate determination and establishes a link between vitamin C and epigenetic regulation

Vitamin C promotes pluripotency of human induced pluripotent stem cells via the histone demethylase JARID1A

Somatic cells can be reprogramed into induced pluripotent stem (iPS) cells by defined factors, which provide a powerful basis for personalized stem-cell based therapies. However, cellular reprograming is an inefficient and metabolically demanding process commonly associated with obstacles that hamper further use of this technology. Spontaneous differentiation of iPS cells cultures represents a significant hurdle that hinder obtaining high quality iPS cells for further downstream experimentation. In this study, we found that a natural compound, vitamin C, augmented pluripotency in iPS cells and reduced unwanted spontaneous differentiation during iPS cells maintenance. Gene expression analysis showed that vitamin C increased the expression of the histone demethylase JARID1A. Furthermore, through gain- and loss-of-function approaches, we show that JARID1A is a key effector in promoting pluripotency and reducing differentiation downstream of vitamin C. Our results therefore highlight a straightforward method for improving the pluripotency and quality of iPS cells; it also shows a possible role for H3K4me2/3 in cell fate determination and establishes a link between vitamin C and epigenetic regulation

A panel of circulating non-coding RNAs in the diagnosis and monitoring of therapy in Egyptian patients with breast cancer

Background: Non-coding RNAs (ncRNAs) have recently been identified to have a pivotal role in many diseases, including breast cancer (BC). This study aims to investigate the relative quantification of long non-coding RNA (lncRNA) H19, microRNA (miR) 675-5p, 675-3p, and miR-let 7 in breast cancer patients. Methods: The study was performed on three groups: Group 1: 30 non-intervened BC female patients about to undergo breast surgery; group 2: 30 postoperative female BC patients about to receive adjuvant anthracycline chemotherapy; and group 3: 30 apparently healthy female volunteers as the control group. Plasma samples were drawn before and after the intervention in groups 1 and 2, with a single sample drawn from group 3. The relative quantification levels were compared with healthy control subjects and were related with the clinicopathological statuses of these patients. Results: There was a statistically significant increase in H19, miR-675-5p, miR-675-3p, and miR-let 7 in the non-intervened BC patients when compared to the control group. Surgery resulted in a significant reduction in all four ncRNAs under investigation. Chemotherapy brought about a significant increase in the level of miR-let 7, with no significant effect on the remaining parameters measured. The assay discriminated normal from BC where a receiver operating characteristic for the area under the curve (ROCAUC) of miR-675-3p showed the maximal AUC of 1.000. The diagnostic sensitivity and specificity were also 100% when CA 15-3 and H19 were combined. Conclusion: The results strongly indicate that the panel of ncRNAs in this study can all potentially act as novel biomarkers whether alone or combined in the diagnosis of BC

A Panel of Circulating Non-Coding RNAs in the Diagnosis and Monitoring of Therapy in Egyptian Patients with Breast Cancer

Background: Non-coding RNAs (ncRNAs) have recently been identified to have a pivotal role in many diseases, including breast cancer (BC). This study aims to investigate the relative quantification of long non-coding RNA (lncRNA) H19, microRNA (miR) 675-5p, 675-3p, and miR-let 7 in breast cancer patients. Methods: The study was performed on three groups: Group 1: 30 non-intervened BC female patients about to undergo breast surgery; group 2: 30 postoperative female BC patients about to receive adjuvant anthracycline chemotherapy; and group 3: 30 apparently healthy female volunteers as the control group. Plasma samples were drawn before and after the intervention in groups 1 and 2, with a single sample drawn from group 3. The relative quantification levels were compared with healthy control subjects and were related with the clinicopathological statuses of these patients. Results: There was a statistically significant increase in H19, miR-675-5p, miR-675-3p, and miR-let 7 in the non-intervened BC patients when compared to the control group. Surgery resulted in a significant reduction in all four ncRNAs under investigation. Chemotherapy brought about a significant increase in the level of miR-let 7, with no significant effect on the remaining parameters measured. The assay discriminated normal from BC where a receiver operating characteristic for the area under the curve (ROCAUC) of miR-675-3p showed the maximal AUC of 1.000. The diagnostic sensitivity and specificity were also 100% when CA 15-3 and H19 were combined. Conclusion: The results strongly indicate that the panel of ncRNAs in this study can all potentially act as novel biomarkers whether alone or combined in the diagnosis of BC

Serum CYFRA 21-1 in Egyptian women with breast cancer

Introduction: Cytokeratin fragment 21.1 (CYFRA 21.1) assay detects a serum fragment of cytokeratin 19 (CK19) and is employed in the diagnosis and management of lung cancer, particularly of squamous cell histotype. Breast carcinoma has been demonstrated to express CK19 fragments in the primary and metastatic lesions and CK19 mRNA is detectable in peripheral blood from patients affected by breast cancer. Aim of the work: The aim of the present study was to evaluate the clinical significance of serum CYFRA21-1 in patients with breast cancer by analyzing the correlation between serum CYFRA21-1 titers, clinicopathological factors and prognosis in comparison with serum CA15.3 and CEA tested in the same samples. Subjects and methods: This study included 60 breast cancer patients and 25 healthy females as control group. Three blood samples were drawn from each patient, before surgery, two weeks after surgery and after 6 cycles of chemotherapy. One blood sample was drawn from each subject of control group. Serum was separated and kept frozen till used for estimation of CYFRA21-1 by enzyme linked immunosorbent assay (ELISA) and serum CA15.3 and CEA by immunoradiometric assay (IRMA). Results: Serum CYFRA21-1 was highly elevated in breast cancer patients than in controls and was significantly associated with tumor size, clinical stage and axillary lymph node involvement. Serum CYFRA21-1 was superior to CA15.3 and CEA as a diagnostic marker for breast cancer using ROC curve analysis. Higher levels of serum CYFRA21-1 and CA15.3 were significantly associated with poor prognosis in primary breast cancer patients. Conclusions: The measurement of serum CYFRA 21-1 in breast cancer patients may be useful for detecting disease relapse and for assessing surgical and chemotherapeutic efficacy. Further prospective studies using greater number of patients are required to confirm our findings