Effect of lncRNA XIST on acute myeloid leukemia cells via miR-142-5p-PFKP axis.

Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.

Calcium response of spatially arranged cell networks to shear stress by confined single cell patterned microfluidic chips.

Osteoblasts in multicellular organisms are sensitive to fluid shear stress (Fss) and respond smartly with versatile patterns of intracellular calcium signal ([Ca2+]i). In this study, a spatial-single cell patterning method was developed by combining micro-contact printing (µCP) and reversible microfluidic chip mounted with vacuum together. Based on this well-defined patterning platform, it's possible to investigate calcium response to Fss modulated by spatial factors, and to characterize multiple calcium patterns quantitatively in terms of cell spacing and cell orientation. The result showed that the Fss-induced [Ca2+]i profiles revealed oscillational signal patterns in non-connected cells such as those in physical-contacted cells. Close-arrayed osteoblasts showed remarkably more [Ca2+]i oscillations than sparse-arrayed cells. The circular shape of the cells was sensitive to oscillational [Ca2+]i as a potential major cause. The consistency of cell orientation and shear stress promoted temporal homogeneity of calcium oscillations.

Clinical Potential of miR-451 and miR-506 as a Prognostic Biomarker in Patients with Breast Cancer.

BACKGROUND: The incidence and mortality of breast cancer in the world remain high. The function and important role of miR-451 and miR-506 in a series of cancers have been proved. The purpose of this research was to explore the clinical diagnosis and prognostic significance of miR-451 and miR-506 expression in breast cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect miR-451 and miR-506 expression in serum and tissues. The relationship of miR-451 and miR-506 with clinical parameters was determined by the chi-square test. Receiver operating characteristics (ROC) analysis was conducted to evaluate the diagnostic accuracy of miR-451 and miR-506 in breast cancer. In addition, we determined the prognostic performance of miR-451 and miR-506 using Kaplan-Meier survival assay. RESULTS: The expression of miR-451 and miR-506 in breast cancer patients was significantly lower than that in healthy people. miR-451 and miR-506 expression decreased in breast cancer tissues compared with paracancerous tissue. High expression of miR-451 and miR-506 was associated with positive lymph node metastasis and late tumor node metastasis stage. Breast cancer patients with high miR-451 and miR-506 expression had lower five-year survival rate. The level of miR-451 and miR-506 expression showed high diagnostic accuracy for distinguishing breast cancer patients and healthy people. CONCLUSION: miR-451 and miR-506 could be used as biomarker for the diagnosis and prognosis of breast cancer.

Expression levels and clinical values of miR-92b-3p in breast cancer.

BACKGROUND: miR-92b is a carcinogenic miRNA that has great potential as a biomarker for disease prognosis, diagnosis, and treatment in the clinic. It is of great significance to analyse the relationship between miR-92b and the clinicopathological characteristics of cancer patients. This paper aimed to investigate the expression levels and clinical values of miR-92b-3p in breast cancer (BC). METHODS: Altogether, 112 female BC patients who were treated in our hospital were included as a study group, and 108 healthy women who came to our hospital for physical examinations were included as a control group. miR-92b-3p expression in the serum of subjects in both groups was detected by fluorescence quantitative PCR (RT-PCR) to analyse the correlation of this miRNA with the patients' pathological features and prognoses. The diagnostic value of miR-92b-3p expression for BC was analysed by plotting a receiver operating characteristic (ROC) curve. RESULTS: miR-92b-3p expression was remarkably higher in the study group (P < 0.05), and its area under the curve (AUC) for detecting BC was 0.88. The expression was correlated with the tumour size, degree of differentiation, TNM staging, and lymphatic metastasis (P < 0.05). miR-92b-3p was significantly positively correlated with the TNM staging (r = 0.40, P < 0.05), was significantly negatively correlated with the degree of differentiation of the breast cancer cells (r = - 0.35, P < 0.05), and was significantly positively correlated with the expression of carbohydrate antigen 125 (CA125) (r = 0.39, P < 0.05). The overall survival rate (OSR) of the 99 patients who had follow-up was 73.74%. The survival status was remarkably better in the low expression group (P < 0.05). miR-92b-3p expression was remarkably higher in the death group (P < 0.05). The AUC of miR-92b-3p alone in the death and survival groups was 0.76. CONCLUSION: miR-92b-3p expression obviously rises in the serum of BC patients and is closely related to the clinical staging, degree of differentiation, and CA125 in BC, so the detection of this miRNA is of great significance to the diagnosis and prognostic evaluation of BC. This miRNA can be used as a potential biomarker for the diagnosis and prognosis of the disease.

A Review of Flavonoids from Cassia Species and their Biological Activity.

Cassia is a large tropical genus with about 600 species that have been widely used as folk medicines in China and India. This genus has been known to possess various biological activities, e.g. antimicrobial, anti-inflammatory, antioxidant, anti-malarial, anti-mutagenic activity, and anti-fertility etc. Flavonoids, for its broad spectrum of pharmacological activity and low toxicity, have attracted more interest in the development and utilization of natural medicines. The structure and biological activity research of flavonoids extracted from Cassia genus is the first step in the search for new drugs from those plants. This review summarizes the isolation and characterization of flavonoids from various Cassia species, such as Cassia absus, Cassia alata, Cassia fistula, etc. Flavonoids can be extracted from different parts of the plants, such as seed, leaf, stem and pod. Chemical structure research of these flavonoids in extracts has revealed many different types of compounds, which show the complication of the metabolism of Cassia genus. The antidiabetic activities can be found in many Cassia species. The efficiency of extraction method and action mode have been widely investigated. The extract not only can reduce the blood glucose level, but also improve glycogen content. Research show that the methanolic extract is effective in inducing hypoglycemic effects in both type I and II diabetes. Because flavonoids have complex structures, various function points, and unknown pertinence and selectivity for different health conditions, there are still many research areas waiting to be explored, such as to reveal the metabolic pathways of flavonoids in the Cassia genus, and to illustrate the structure-activity relationship between flavonoids and protein. That above-mentioned research will provide the basis for further medicinal development on this genus.

[Relationship between clinical features and prognosis of highly pathogenic avian influenza A/H5N1 infection in humans in mainland China].

OBJECTIVE: To investigate the relationship between clinical features of patients with A/H5N1 infection and their prognosis in mainland China. METHODS: This study included 28 human cases with A/H5N1 infection in mainland China from October 2005 to May 2008. Data were collected and reviewed from hospital medical records and publishied papers. A database was built by EPIDATA 3.02 and statistical analyses were performed with SPSS 13.0. RESULTS: The median age of the 28 cases was 29 years (range 6-62), and 15 were females. Ten patients survived, and 18 died. The typically clinical manifestations of human influenza A/H5N1 infection included fever and lower respiratory infection. The numbers of peripheral white blood cells, lymphocytes and platelets in the survival and non-survival groups were (4.01 +/- 1.86) x 10(9)/L vs (5.1 +/- 2.9) x 10(9)/L, (1.09 +/- 0.49) x 10(9)/L vs (0.98 +/- 0.44) x 10(9)/L, and (116 +/- 39) x 10(9)/L vs (101 +/- 40) x 10(9)/L, respectively; the differences were not statistically significant between the 2 groups (P>0.05). There was also no statistically significant difference in the increased serum enzymes, such as aspartate aminotransferase [(173 +/- 246) U/L vs (272 +/- 263) U/L], lactate dehydrogenase [(1016 +/- 568) U/L vs (1512 +/- 1052) U/L], creatine kinase [(1099 +/- 1590) U/L vs (2534 +/- 4281) U/L] and MB isoenzyme of creatine kinase [(28 +/- 30) U/L vs (125 +/- 197) U/L] (P>0.05) between the survival and the non-survival groups. However, there was a statistically significant difference in the number of patients with an initial LDH level more than 8 fold of the normal value between the survival and the non-survival groups (none vs 6, P<0.05). All of the 28 cases developed bilateral multiple infiltrates and consolidation in chest radiographs. Acute respiratory distress syndrome occurred in 22 cases, 17 of them died. All the 9 patients with acute kidney injury died. Ten patients received antiviral treatment with oseltamivir, and 6 of them survived. There was a statistical difference in the time of initiating oseltamivir treatment between the survival and the non-survival cases [(6.5 +/- 3.0) d vs (11.8 +/- 3.3) d, Z = 3.70, P<0.05]. Broad spectrum antibiotics and corticosteroids were administered in all of the 28 cases. There was no statistical difference between the survival and the non-survival groups regarding to the corticosteroid treatment (P>0.05). CONCLUSIONS: Initial LDH level reaching more than 8 fold of the normal value suggests a poor prognosis for human H5N1 infection. Patients complicated with either ARDS or acute kidney injury had a higher risk of death. Early administration of effective antiviral agents might improve the prognosis and decrease case fatality.

[Clinical characteristic analysis of the first human case infected by influenza A (H5N1) in Jiangxi Province].

OBJECTIVE: To describe the clinical, laboratory and radiological presentation of a human case infected by influenza A (H5N1), and to understand its management and prognosis. METHODS: The clinical and autopsy data of the first human case infected by influenza A (H5N1) in Jiangxi Province were collected and analyzed. RESULTS: The first case infected by influenza A (H5N1) in Jiangxi Province was confirmed by laboratory findings with reverse transcription-polymerase chain reaction (RT-PCR) and influenza A (H5N1) isolation. The patient had been healthy in the past and exposed to the environment of bird flu before illness. The initial symptoms included high fever with influenza-like symptoms, and then cough and purulent sputum mixed with blood appeared. The clinical situation deteriorated progressively with occurrence of diarrhea and dyspnea. Laboratory abnormalities included decrease of peripheral white blood cells and lymphocytes, urine protein, dramatic increase of enzymes associated with hepatic injury and myocarditis and decrease of serum albumin. Six days later, penicillin-resistant streptococcus pneumoniae was isolated from multiple sputum cultures. With the deterioration of clinical situation, several other bacteria and fungi were found in sputum culture. Pulmonary infiltrates were evident in right middle and lower lobe at day 5 after illness, and rapidly progressed to involve bilateral lungs as acute respiratory distress syndrome (ARDS)-like changes. The patient was treated with antiviral, antibacterial, and antifungal reagents, and corticosteroids and invasive mechanical ventilation were also administered, but without any improvement. The patient died 27 days after the onset of symptoms and an autopsy was performed. Pathologically, the lungs exhibited diffuse alveolar damage. The lymphocytes in the spleen, the lymph nodes and the tonsils were depleted prominently with histiocytic hyperplasia and hemophagocytic phenomena. Edema and degeneration of myocytes in the heart and extensive acute tubular necrosis in the kidney were observed. CONCLUSION: The prognosis was very poor if influenza A (H5N1) infected human cases was developed as ARDS with multiple organ damage or failure.