Jinzhong Xu

HOTAIR may regulate proliferation, apoptosis, migration and invasion of MCF-7 cells through regulating the P53/Akt/JNK signaling pathway

Breast cancer is a common malignancy, and it is the second leading cause of cancer-related death among women worldwide. The pathogenesis of breast cancer is poorly understood, leading to unsatisfactory efficacy of current anti-PC therapies. The aim of this study is to investigate the role of LncRNA HOTAIR in proliferation, apoptosis, migration and invasion of human breast cancer cell line MCF-7. MCF-7 cells were cultured and transfected with HOTAIR siRNA, and the proliferation rate of cells was determined using MTT and colony-forming assay; moreover, the apoptosis as well as cell cycles were determined using annexin V/propidium iodide staining methods and analyzed using flow cytometery; furthermore, cell scratch and transwell assays have been performed to examine the migration and invasion of MCF-7 cells; Next, cells were collected, and RT-qPCR as well as western blotting assay were performed to examine the expression of P53, MDM2, AKT, JNK, MMP-2 and MMP-9. We discovered that knockdown of HOTAIR induced significant decrease in proliferation and increase in apoptosis of MCF-7 cells, and the cell cycles of HOTAIR siRNA transfected cells have been arrested at G1 phase (p<0.01); moreover, knockdown of HOTAIR lead to marked decrease in the migration and invasion ability of MCF-7 cells; finally, knockdown of HOTAIR induced significant decrease in the expression of P53/Akt/JNK (p<0.01), and significant increase in the expression of P53 in MCF-7 cells (p<0.01). In conclusion, our results proved that HOTAIR may regulate proliferation, apoptosis, migration and invasion of MCF-7 cells through regulating the P53/Akt/JNK signaling pathway.

Celecoxib prevents pressure overload‐induced cardiac hypertrophy and dysfunction by inhibiting inflammation, apoptosis and oxidative stress

To explore the effects of celecoxib on pressure overload‐induced cardiac hypertrophy (CH), cardiac dysfunction and explore the possible protective mechanisms. We surgically created abdominal aortic constrictions (AAC) in rats to induce CH. Rats with CH symptoms at 4 weeks after surgery were treated with celecoxib [2 mg/100 g body‐weight(BW)] daily for either 2 or 4 weeks. Survival rate, blood pressure and cardiac function were evaluated after celecoxib treatment. Animals were killed, and cardiac tissue was examined for morphological changes, cardiomyocyte apoptosis, fibrosis, inflammation and oxidative stress. Four weeks after AAC, rats had significantly higher systolic, diastolic and mean blood pressure, greater heart weight and enlarged cardiomyocytes, which were associated with cardiac dysfunction. Thus, the CH model was successfully established. Two weeks later, animals had impaired cardiac function and histopathological abnormalities including enlarged cardiomyocytes and cardiac fibrosis, which were exacerbated 2 weeks later. However, these pathological changes were remarkably prevented by the treatment of celecoxib, independent of preventing hypertension. Mechanistic studies revealed that celecoxib‐induced cardiac protection against CH and cardiac dysfunction was due to inhibition of apoptosis via the murine double mimute 2/P53 pathway, inhibition of inflammation via the AKT/mTOR/NF‐κB pathway and inhibition of oxidative stress via increases in nuclear factor E2‐related factor‐2‐mediated gene expression of multiple antioxidants. Celecoxib suppresses pressure overload‐induced CH by reducing apoptosis, inflammation and oxidative stress.

Impact of low hemoglobin on the development of contrast-induced nephropathy: A retrospective cohort study

An increase in the use of iodinated contrast media, such as iohexol, iodixanol, iopamidol and iopromide, occasionally causes contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). The present study aimed to assess the effects of low levels of hemoglobin on the development of CIN in patients with normal renal function following CAG/PCI. A total of 841 consecutive patients undergoing CAG/PCI were divided into two groups: Patients with low levels of hemoglobin (male, <120 g/l; female, <110 g/l; n=156) and normal levels of hemoglobin (male, 120–160 g/l; female, 110–150 g/l; n=685). Multiple logistic regression analysis was performed to identify risk factors for CIN, which developed in 14.7% of patients with low levels of hemoglobin (relative risk, 3.07) and 5% of patients with normal levels of hemoglobin (P<0.01). Independent risk factors for developing CIN in patients with low levels of hemoglobin were a contrast media volume ≥200 ml, diuretic usage, low levels of hemoglobin and diabetes mellitus. For the patients with normal hemoglobin levels, the independent risk factors for developing CIN were a contrast media volume ≥200 ml and diuretic usage. The change in serum creatinine in patients with low levels of hemoglobin was significantly greater compared with patients with normal levels of hemoglobin (7.35±22.60 vs. 1.40±12.00; P<0.01). A similar incidence of developing CIN was observed when patients were administered each type of contrast media: Iohexol, iodixanol, iopamidol and iopromide. The optimal cut-off point at which the serum hemoglobin concentration resulted in a high probability of developing CIN was determined as 111.5 g/l in females and 115.5 g/l in males. In conclusion, low levels of hemoglobin were observed to be an independent risk factor for developing CIN. Patients with reduced hemoglobin levels should, therefore, be closely monitored prior to, and during, the administration of iodinated contrast media.

Molecular characterization of a pedigree carrying the hypertension‑associated mitochondrial tRNAGln T4363C mutation

Mitochondrial DNA mutations have been reported to be associated with essential hypertension. The present study reported the clinical and molecular features of a Chinese pedigree with maternally inherited hypertension. A total of 6 matrilineal relatives in this pedigree presented with variable degrees of hypertension; the age of onset ranged between 39 and 63 years, and the average age of onset was 53 years. Analysis of the mitochondrial genome in members of this family demonstrated the occurrence of a homoplasmic T4363C mutation in the transfer (t)RNAGln gene and 25 genetic polymorphisms belonging to mitochondrial haplogroup B4. Notably, the T4363C mutation was localized at the anticodon stem of tRNAGln, which is highly conserved across various species (conventional position 38). To determine its potential pathogenicity, RNA Fold software was used to predict the secondary structure of tRNAGln with and without this mutation. The results indicated that the T4363C mutation induced a significant alteration in the secondary structure of tRNAGln, and may reduce the steady-state levels of tRNAGln. Furthermore, matrilineal relatives carrying the T4363C mutation exhibited different age of onset and variable degrees of blood pressure, thus indicating that the T4363C mutation itself was insufficient to produce the clinical phenotype. Therefore, other modified factors, including environmental factors, and nuclear gene and epigenetic modifications, may be involved in the pathogenesis of hypertension. In conclusion, the present study provided valuable information regarding the association between tRNA mutations and hypertension.

Cerebrospinal fluid FGF23 levels correlate with a measure of impulsivity

Fibroblast growth factor 23 (FGF23) is a bone-derived protein produced mainly by osteocytes and osteoblasts and at low levels in specific parts of the brain. It has been shown to associate with mood regulation. Lithium treatment gives rise to significant elevations of serum FGF23 levels in depressive patients. High peripheral blood FGF23 levels correlated with poor cognitive performance in hemodialysis patients. However, no direct evidence demonstrates a relationship between FGF23 and mood regulation. In this study, we aimed to measure the concentration of cerebrospinal fluid (CSF) FGF23 and to explore its relationship with a cluster of emotional characteristics. We measured CSF FGF23 levels in 96 male Chinese subjects. All subjects completed the Chinese version of the Barratt Impulsiveness Scale (BIS 11), the Beck Depression Inventory (BDI) and the Self-Rating Anxiety Scale (SAS). CSF FGF23 levels ranged from 12.8 to 99.3 pg/mL. Negative correlations were found between CSF FGF23 concentrations and BIS non-planning, BIS cognition and BIS total score (all p < 0.05). Nevertheless, except for the BIS cognition scores, these correlations became insignificant after Bonferroni correction. No correlations were found between CSF FGF23 concentrations and BDI or SAS scores. These findings suggest that CSF FGF23 levels correlate with a measure of impulsivity.

CSF glutamate level decreases in heavy smokers and negatively correlates with BDI scores

Glutamate is involved in mental disorders and nicotine addiction. The aim of the present study was to evaluate the relationship between cerebrospinal fluid (CSF) glutamate levels and mental status in Chinese heavy smokers. Participants comprised 41 non-smokers and 77 heavy smokers (n = 118). Cerebrospinal fluid was extracted and glutamate levels were measured. We recorded age, years of education, BMI, the Barratt impulsiveness scale (BIS), the Beck Depression Inventory (BDI) and the Self-Rating Anxiety Scale (SAS). BIS action scores, total scores and BDI scores were significantly different between the groups. Partial correlation analyses with age and education years as covariates found that CSF glutamate levels negatively correlated with BDI scores, but did not correlate with SAS scores in heavy smokers. No correlation was found between CSF glutamate levels and BDI or SAS scores in non-smokers. In conclusion, heavy smokers had more impulsivity had lower levels of CSF glutamate and higher BDI scores. CSF glutamate levels negatively correlated with BDI scores in heavy smokers.

Negative correlation between CSF lactate levels and MoCA scores in male Chinese subjects

Lactate is a product of glycolysis by astrocytes and can be generated as a primary metabolic energy source by neurons. Lactate plays multifunctional role in human brain energy metabolism and cognitive function. However, no direct evidence demonstrated the link between lactate and cognition in normal condition. In the present study, concentrations of lactate in cerebrospinal fluid (CSF) and peripheral blood were measured to investigate the association of lactate with cognitive ability, which was assessed by Montreal Cognitive Assessment (MoCA), in 99 male Chinese subjects. Correlation analyses revealed that serum lactate levels were negatively correlated with age, and CSF lactate levels were negatively correlated with MoCA scores after Box-Cox transformations. But no correlation was found between serum lactate levels and MoCA scores after Box-Cox transformations. In conclusion, the results indicate that CSF lactate levels were negatively correlated with MoCA scores in male Chinese subjects.