Tohoku Journal of Experimental Medicine最新文献

Early childhood caries (ECC) is common in children. Little is known about the genetic association of the methionine synthesis reductase (MTRR) gene rs1801394 and methionine synthetase (MTR) gene rs1805087 polymorphisms with ECC, which was examined in the Chinese Han population. Genotyping was performed using the buccal mucosa from 150 normal and 150 ECC children. For genotype and allele distribution comparison, Chi-square test and multiple logistic regression analysis were performed. The odd ratio (OR) and 95% confidence interval (CI) were calculated. MTR gene rs1805087 AG genotype distribution in the ECC group was clearly different from the control group (P = 0.029), and the ECC risk in cases with AG genotype was 0.525 times lower than those carrying AA genotype (95% CI = 0.292-0.942). Logistic regression analysis after adjustment for other clinical indicators determined that the MTR gene rs1805087 AG genotype was still strongly associated with susceptibility to ECC (OR = 0.499, 95% CI = 0.273-0.913, P = 0.024). Significant association was also seen for sugary food intakes (OR = 1.965, 95% CI = 1.162-3.321, P = 0.012), tooth brushing (OR = 0.569, 95% CI = 0.356-0.924, P = 0.023) and sex (OR = 0.562, 95% CI = 0.349-0.907, P = 0.018) with ECC risk. No notable genetic association was found between MTRR gene rs1801394 polymorphism and ECC risk. MTR gene rs1805087 polymorphism may aggrandize the susceptibility to ECC, and AA genotype appeared to be a dangerous element for the development of ECC.

Septic acute kidney injury (AKI) is a common complication in critically ill patients with high morbidity and mortality. This study intends to clarify the clinical value and molecular mechanism of microR-380-3p in septic AKI by recruiting patients with septic AKI and establishing septic AKI cell models. Patients with septic AKI were included and human kidney-2 (HK-2) cells were induced by lipopolysaccharide (LPS) to construct the AKI cell model of sepsis. The expression of microR-380-3p was detected by quantitative real-time RT-PCR (qRT-PCR). The expression of Bax, cleaved caspase 3, Bcl-2, p65, and p-p65 was detected by Western blot. The contents of inflammation and oxidation were determined by commercial kits. Bioinformatics predicted the binding target of microR-380-3p and a dual luciferase reporting system was used to verify the regulatory relationship between microR-380-3p and RAP1B. The concentration of microR-380-3p was elevated in patients with septic AKI and appeared to be a biomarker for these patients. Silenced microR-380-3p reversed the damage of LPS on HK-2 cells via promoting viability, inhibiting apoptosis, inflammation, and oxidation. RAP1B was a target of microR-380-3p and microR-380-3p exerted targeted inhibition of RAP1B expression level. Down-regulation of RAP1B reversed the influence of silenced microR-380-3p on HK-2 cells. MicroR-380-3p/RAP1B participated in activating the NF-κB pathway. MicroR-380-3p down-regulated RAP1B to exacerbate septic AKI, providing a potential therapeutic biomarker for septic AKI.

Indium lung is an occupational lung disease caused by exposure to indium-tin-oxide (ITO) dust. Compared to other occupational lung diseases, indium lung has a shorter latency period and the respiratory status continues to worsen even after exposure to the work environment improves. Paraseptal emphysema which affects mainly the subpleural area is seen on chest images obtained via computed tomography (CT), regardless of the smoking history. However, the pathogenesis of emphysema in indium lung is still unclear. Therefore, we re-evaluated the pathology of three previously reported cases of indium lung. Paraseptal emphysema was observed in both smokers and nonsmokers. Obstructive respiratory impairment worsened over time in the cases with paraseptal emphysema. Many alveolar walls were destroyed independent of the presence or absence of emphysetamous changes or fibrosis. Moreover, bronchiolitis was found to be less common in indium lung than in asbestosis (the most common occupational lung disease) or common cases of chronic obstructive pulmonary disease caused by smoking. It has been shown that ITO causes protease anti-protease imbalance, oxidant-antioxidant imbalance, and continuous, abnormal inflammation (the three major causes of emphysema). In addition, nano-sized ITO is less likely to be trapped in the upper airways and may easily reach the subpleural alveoli. Furthermore, ITO may continue to cause sustained tissue injury at the alveolar level potentially resulting in emphysema. Further studies are needed to elucidate the detailed pathogenesis of indium lung by comparing it with other occupational lung diseases.

MicroRNAs (miRNAs) are related to the regulation of bone metabolism. Delayed fracture healing (DFH) is a common complication after fracture surgery. The study attempted to examine the role of miR-98-5p and bone morphogenetic protein (BMP)-2 with the onset of DFH. A total of 140 patients with femoral neck fracture were recruited, including 80 cases with normal fracture healing (NFH) and 60 cases with DFH. MC3T3-E1 cells were induced cell differentiation for cell function experiments. Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to test mRNA levels. Cell proliferation and apoptosis were determined via CCK-8 and flow cytometry assay. Luciferase reporter assay was done to verify the targeted regulatory relationship of miR-98-5p with BMP-2. In comparison with NFH cases, DFH patients owned high levels of serum miR-98-5p and low concentration of BMP-2, and the levels of the two indexes are significantly negatively correlated. Both miR-98-5p and BMP-2 had the ability to predict DFH, while their combined diagnostic value is the highest. BMP-2 was demonstrated to be the target gene of miR-98-5p. Overexpression of BMP-2 reversed the role of miR-98-5p in MC3T3-E1 cell proliferation, apoptosis and differentiation. Increased miR-98-5p and decreased BMP-2 serve as potential biomarkers for the diagnosis of DFH. MiR-98-5p overexpression inhibits osteoblast proliferation and differentiation via targeting BMP-2.

Depression disorder has become a major mental disease and has attracted special attention globally. Identifying specific biomarkers for the diagnosis and severity of depression disorder would benefit its clinical management. This study focused on the significance of lncRNA SNHG14 in depression disorder and investigated its effect on depression-like behaviors, aiming to explore a potential biomarker for depression disorder occurrence and development. This study included 147 patients with depression disorder and 98 healthy individuals. The serum SNHG14 in all participants was analyzed by PCR, and its diagnostic value was evaluated by receiver operatorating characteristic curve (ROC) analysis. The depression-like behaviors were induced via chronic social defeat stress (CSDS) and evaluated by sucrose preference, forced swimming, and open field tests. SNHG14 was significantly upregulated in depression disorder patients relative to healthy individuals, which discriminated depression disorder patients with a relatively high efficiency. Depression disorder patients with severe conditions showed higher serum SNHG14 levels, and a significantly positive correlation of SNHG14 with PHQ9 score was demonstrated. In CSDS mice, increasing SNHG14 and decreasing miR-200a-3p were observed. Silencing SNHG14 and overexpressing miR-200a-3p could alleviate reduced sucrose preference, increased swimming immobility time, decreased standing times, and decreased traveling distance induced by CSDS. The knockdown of SNHG14 promoted the expression of miR-200a-3p, and silencing miR-200a-3p could reverse the protective effect of SNHG14 silencing on depression-like behaviors. SNHG14 served as a biomarker for the occurrence and severity of depression disorder. Silencing SNHG14could alleviate depression-like behaviors via modulating miR-200a-3p.