[Effect and mechanism of microRNA-155 in chronic obstructive pulmonary disease by targeting PIK3R1].

This study aimed to investigate the effect of microRNA-155 (miR-155) in chronic obstructive pulmonary disease (COPD) and cigarette smoke extract (CSE)-treated airway smooth muscle cells (ASMCs) by targeting phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to regulate the PTEN/PI3K/Akt signaling pathway. The COPD mouse model was induced by lipopolysaccharide (LPS) combined with passive smoking. After modeling, miR-155 mimics and miR-155 inhibitor were used for intervention treatment. The pulmonary function of each group was detected by an EMKA detector. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and scores of lung tissues. The expression of TNF-α, IL-6, and IL-1ß in bronchial alveolar lavage fluid (BALF) was detected by ELISA. Primary ASMCs were isolated and cultured in adherent tissue culture. The proliferation activity was detected by CCK-8 and EdU assays. Transwell and wound healing assays were used to measure the migration of ASMCs. The targeting relationship between miR-155 and PIK3R1 was validated by a double luciferase reporter gene assay. The expression levels of miR-155 and PIK3R1 mRNA in lung tissues of mice in each group were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was used to detect the expression levels of Ki67, PNCA, PTEN, p-PI3K, PI3K, p85α, p-Akt, and Akt in lung tissues and ASMCs. The results showed that lung function was significantly reduced in the miR-155 mimic group, and the levels of PIK3R1 were significantly increased; while lung function in the miR-155 inhibitor group was significantly improved. The results of HE staining showed that there was obvious inflammatory cell infiltration in the miR-155 mimics group compared to that of the model group. Lung histopathological injury was significantly reduced in the miR-155 inhibitor group, accompanied by decreased expression of Ki67, PNCA, PI3K, p-Akt, increased PTEN and p85α protein levels, and reduced levels of TNF-α, IL-6, and IL-1ß in BALF. The results of the double luciferase reporter gene assay showed that miRNA-155 could target bind to PIK3R1. Compared with those in the CSE+miR-155 NC group, the proliferation and migration of ASMCs were significantly increased in the CSE+miR-155 group. The proliferation and migration of ASMCs were significantly attenuated in the CSE+miR-155+pcDNA PIK3R1 group compared with those in the CSE+miR-155 group, accompanied by decreased expression of Ki67, PNCA, p-Akt and increased PTEN and p85α protein levels. These results suggest that miR-155 activates the PTEN/PI3K/Akt signaling pathway by targeting PIK3R1 to promote the occurrence and development of COPD, which provides new evidence for the use of miR-155 in the treatment of COPD.

Nomogram for predicting prolonged postoperative ileus in colorectal cancer based on age and inflammatory markers.

Aim: To explore the relationship between inflammatory markers and prolonged postoperative ileus (PPOI), and to establish a nomogram for predicting PPOI. Patients & methods: The data of 229 patients were analyzed retrospectively. Univariate and multivariate logistic regression analysis were used to analyze the risk factors affecting the occurrence of PPOI. The predictive model of PPOI was established and verified internally. Results: Postoperative PPOI occurred in 87 (38.0%) of all 229 patients. Our study showed that age, preoperative neutrophil-lymphocyte ratio and changes in neutrophil-lymphocyte ratio were independent risk factors for PPOI. Conclusion: The nomograms established based on these independent risk factors have good predictive efficacy and may be able to guide clinicians to individualize the diagnosis and treatment.

Crystal Structure of Inorganic Pyrophosphatase From Schistosoma japonicum Reveals the Mechanism of Chemicals and Substrate Inhibition.

Soluble inorganic pyrophosphatases (PPases) are essential for facilitating the growth and development of organisms, making them attractive functional proteins. To provide insight into the molecular basis of PPases in Schistosoma japonicum (SjPPase), we expressed the recombinant SjPPase, analyzed the hydrolysis mechanism of inorganic pyrophosphate (PPi), and measured its activity. Moreover, we solved the crystal structure of SjPPase in complex with orthophosphate (Pi) and performed PPi and methylene diphosphonic acid (MDP) docking into the active site. Our results suggest that the SjPPase possesses PPi hydrolysis activity, and the activity declines with increased MDP or NaF concentration. However, the enzyme shows unexpected substrate inhibition properties. Through PPi metabolic pathway analysis, the physiological action of substrate inhibition might be energy saving, adaptably cytoprotective, and biosynthetic rate regulating. Furthermore, the structure of apo-SjPPase and SjPPase with Pi has been solved at 2.6 and 2.3 Å, respectively. The docking of PPi into the active site of the SjPPase-Pi complex revealed that substrate inhibition might result from blocking Pi exit due to excess PPi in the SjPPase-Pi complex of the catalytic cycle. Our results revealed the structural features of apo-SjPPase and the SjPPase-Pi complex by X-ray crystallography, providing novel insights into the physiological functions of PPase in S. japonicum without the PPi transporter and the mechanism of its substrate inhibition.

High expression of the TEFM gene predicts poor prognosis in hepatocellular carcinoma.

BACKGROUND: Mitochondrial transcription elongation factor (TEFM) is an essential molecule that regulates the replication-transcription switch of mitochondrial DNA. TEFM modulates both transcription elongation and RNA processing in mitochondria. The purpose of the present study was to determine the association of TEFM with tumor progression and prognosis in hepatocellular carcinoma (HCC) patients. METHODS: The different protein expression level of TEFM among HCC cell lines was detected by Western blotting. The gene expression profiling interactive analysis (GEPIA) was used to dynamically analyze the mRNA expression of TEFM gene in different stages of HCC. The protein and mRNA expression levels of TEFM were detected by immunohistochemistry, Western blotting and qRT-PCR. The mRNA-SeqV2 expression of TEFM and clinical information of HCC patients were downloaded from the TCGA database by using R3.6.3 software. Next, the relationships between the expression level of TEFM and clinicopathological characteristics and the prognostic value of TEFM were analyzed. A Cox regression model was used for multivariate analysis of the factors that affected the prognosis of HCC. Finally, the association between the expression levels of TEFM and other mitochondrial regulatory genes and HCC biomarker genes was analyzed by GEPIA. RESULTS: TEFM is upregulated in HCC cell lines compared to noncancerous liver cell line. TEFM protein and mRNA expression levels in HCC tissues were significantly upregulated compared with those in noncancerous liver tissues. In addition, the mRNA expression level of TEFM was significantly correlated with sex, serum AFP level, and vascular invasion (P<0.05). Further analysis showed that high expression level of TEFM was unfavorable in terms of the prognosis of patients with HCC. Cox multivariate regression analysis showed that patient age, vascular invasion, and TEFM expression were independent factors affecting the prognosis of HCC patients (P<0.05). The expression level of the TEFM gene was significantly positively correlated with the expression of multiple mitochondrial regulatory genes and biomarker genes of HCC (P<0.01, R>0). CONCLUSIONS: Our findings reveal that TEFM may play an important role in the progression of HCC. More importantly, the elevated expression of TEFM may potentially predict poor overall survival (OS) and disease-free survival (DFS) in patients with HCC.

[Evolution and Evaluation of O3 and VOCs in Zhengzhou During the National Traditional Games of Ethnic Minorities Period].

During the National Traditional Games of Ethnic Minorities (NTGEM) 2019, air quality in Zhengzhou was analyzed to evaluate the impact of pollution prevention and control measures on Zhengzhou. Ground-observed meteorological and pollutant data as well as the chemical compositions of volatile organic compounds (VOCs) were investigated. The results showed that the six parameters of pollutants in the safeguard period in 2019 indicated a downward trend as compared with that during the same time in 2018, and the average concentrations of PM2.5 and PM10 were decreased by 16.2% and 25.1%, respectively. However, the average concentration of O3 was only reduced by 3.7%. The daily proportions of primary pollutants of O3 increased to 90% during the NTGEM, and the ozone pollution was severe in this period. Meanwhile, the concentration of total volatile organic compounds (TVOCs) in the safeguard period was 26.21×10-9, which was significantly lower than that during the historical period. Six emission sources of the VOCs were identified using PMF model, including vehicle exhaust (28%), LPG evaporation (21%), combustion source (16%), industrial emissions (15%), solvent utilization (15%), and biogenic VOCs (5%). During the NTGEM period, the control of combustion sources and industrial sources was evident.

Expression of MTERF3 gene in breast carcinoma and the relationship with clinicopathological characteristics.

BACKGROUND: Mitochondrial transcription termination factor 3 (MTERF3) is a negative regulator of mitochondrial transcription. It is a modular factor involves in mitochondrial ribosome biogenesis and protein synthesis. However, the association between MTERF3 and breast cancers remains largely unknown. The aim of this study was to investigate the expression of MTERF3 in breast carcinoma and to analyze its clinicopathological significance, and to examine the potential prognostic value of MTERF3 in breast cancer. METHODS: The protein expression levels of MTERF3 in MCF7 (Luminal A), BT-474 (Luminal B), SKBR3 (HER2 overexpression), MDA-MB-468 (Basal like) and MCF10A cell lines were detected by Western blotting. Immunohistochemistry (IHC), Western blotting, and semiquantitative RT-PCR were performed to analyze the protein and mRNA expression levels of MTERF3 in 58 breast cancer tissues and 58 noncancerous breast tissues. The MTERF3 expression data and clinical information from breast cancer patients were downloaded from the TCGA dataset by using the R3.6.1 software. Then the relationship between the expression level of MTERF3 and clinicopathological characteristics and the prognostic value was analyzed. A Cox regression model was performed for the multivariate analysis of the factors that affected the prognosis of breast cancer. The association between the expression levels of MTERF3 and other mitochondrial regulatory genes was analyzed with GEPIA. RESULTS: MTERF3 is upregulated in breast cancer cell lines compared to noncancerous breast cell line. The IHC results showed that the MTERF3 protein was located in the cytoplasm, and the rate of positive expression in breast cancer tissue was significantly upregulated compared with the adjacent normal tissue. The mRNA and protein expression levels of MTERF3 in breast cancer tissues were significantly higher than that in breast tissues. Moreover, the expression of MTERF3 was significantly correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site (P<0.05). Further analysis showed MTERF3 expression was not related to prognosis. Multivariate Cox regression analysis showed that age, metastasis status and tumor type were independent prognostic factors for breast cancer patients. The expression levels of MTERF3 were positively correlated with the TFAM, TFB1M, TFB2M, MTERF1, TEFM and MFN1 genes but negatively correlated with the MTERF4 and PINK1 genes. In addition, the expression levels of MTERF3 were not correlated with the MTERF2 gene. CONCLUSIONS: MTERF3 was significantly upregulated in breast cancer cells and tissues compared with noncancerous cells and tissues. Moreover, the expression level of MTERF3 was correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site. These findings suggested that the upregulation of MTERF3 may be used as a diagnostic and therapeutic target in breast carcinoma.

Large vein injection alleviates rocuronium-induced pain in gynaecologic patients.

BACKGROUND: Rocuronium-induced pain upon injection is very common in the clinical setting. Using the antecubital rather than the hand vein can avoid pain due to propofol injection. We aimed to investigate whether the use of the antecubital vein for injection would alleviate rocuronium-induced pain in a similar fashion. METHODS: Sixty patients (ASA classes I and II) scheduled for gynaecologic laparoscopy were randomised into two groups. Rocuronium (0.6mg/kg) was injected either into the vein on the dorsum of the hand (group D) or a large vein in the antecubital fossa (group A). Pain was assessed and recorded using a four-point scale. RESULTS: Compared with group D, the incidence of pain and severe pain was lower in group A patients. The rate of no pain was also higher in group A patients. CONCLUSION: The incidence and severity of rocuronium-induced injection pain were significantly alleviated via use of a large vein for rocuronium injection.