A novel NSUN5/ENO3 pathway promotes the Warburg effect and cell growth in clear cell renal cell carcinoma by 5-methylcytosine-stabilized ENO3 mRNA.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) cells often reprogram their metabolisms. Enolase 3 (ENO3) is closely related to the Warburg effect observed in cells during tumor progression. However, the expression and function of ENO3 in ccRCC cells remain unclear. Therefore, this study investigated the expression and functional significance of ENO3 in the Warburg effect observed in ccRCC cells. METHODS: In this study, B-mode and microflow imaging ultrasound examinations were performed to evaluate patients with ccRCC. The extracellular acidification rate test and glucose uptake and lactate production assays were used to examine the Warburg effect in ccRCC cells. Western blotting, quantitative reverse transcription polymerase chain reaction, and immunochemistry were used to detect the expression of ENO3 and NOP2/Sun RNA methyltransferase 5 (NSUN5). RESULTS: ENO3 upregulation in ccRCC tumor tissues was accompanied by an increase in tumor size. Importantly, ENO3 participated in the Warburg effect observed in ccRCC cells, and high levels of ENO3 indicated a poor prognosis for patients. Loss of ENO3 reduced glucose uptake, lactate production, and extracellular acidification rate as well as inhibited ccRCC cell proliferation. Furthermore, NSUN5 was involved in the ENO3-regulated Warburg effect and ccRCC cell progression. Mechanically, NSUN5 was upregulated in ccRCC tissues, and NSUN5 upregulation mediated 5-methylcytosine modification of messenger RNA (mRNA) in ccRCC cells to promote mRNA stability and ENO3 expression. CONCLUSIONS: Collectively, the destruction of the NSUN5/ENO3 axis prevents ccRCC growth in vivo and in vitro, and targeting this pathway may be an effective strategy against ccRCC progression.

Effects of Organophosphate-Degrading Bacteria on the Plant Biomass, Active Medicinal Components, and Soil Phosphorus Levels of Paris polyphylla var. yunnanensis.

Paris polyphylla var. yunnanensis, a medicinal plant that originated in Yunnan (China), has been over-harvested in the wild population, resulting in its artificial cultivation. Given the negative environmental impacts of the excessive use of phosphorus (P) fertilization, the application of organophosphate-degrading bacteria (OPDB) is a sustainable approach for improving the P use efficiency in Paris polyphylla var. yunnanensis production. The present work aimed to analyze the effects of three organic phosphate-solubilizing bacteria of Bacillus on the yield and quality of P. polyphylla var. yunnanensis and the P concentrations in the soil. All the inoculation treatments distinctly increased the rhizome biomass, steroidal, and total saponin concentrations of the rhizomes and the Olsen-P and organic P in the soil. The highest growth rate of rhizomes biomass, steroidal saponins, available phosphorus, and total phosphorus content was seen in the S7 group, which was inoculated with all three OPDB strains, showing increases of 134.58%, 132.56%, 51.64%, and 17.19%, respectively. The highest total saponin content was found in the group inoculated with B. mycoides and B. wiedmannii, which increased by 33.68%. Moreover, the highest organic P content was seen in the group inoculated with B. wiedmannii and B. proteolyticus, which increased by 96.20%. In addition, the rhizome biomass was significantly positively correlated with the saponin concentration, together with the positive correlation between the Olsen-P and organic P and total P. It is concluded that inoculation with organophosphate-degrading bacteria improved the biomass and medicinal ingredients of the rhizome in P. polyphylla var. yunnanensis, coupled with increased soil P fertility, with a mixture of the three bacteria performing best.

[Tanshinone IIa attenuates vascular calcification through inhibition of NF-κB and ß-catenin signaling pathways].

Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and ß-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and ß-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and ß-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.

Utility of lung ultrasound to identify interstitial lung disease: An observational study based on the STROBE guidelines.

ABSTRACT: Lung ultrasound (LUS) has recently been used to identify interstitial lung disease (ILD). However, data on the role of LUS in the detection of ILD remain limited. The aim of this study was to investigate the diagnostic value of LUS compared with high-resolution computed tomography (HRCT) in patients with ILD.The retrospective study was carried out by reviewing the medical records of patients with respiratory signs and symptoms discharged from the respiratory ward. Only patients with suspected ILD who underwent HRCT and LUS within a week were selected. ILD was identified with a semi-quantitative score of B-lines >5 and a Warrick score >0 points. The endpoints of LUS in diagnosing ILD (i.e., sensitivity, specificity, positive likelihood ratio [PLR], negative likelihood ratio [NLR], positive predictive value [PPV], and negative predictive value [NPV], and receiver operating characteristic [ROC] curve) was compared with that of HRCT. The reference standard used for the diagnosis of ILD was based on history, clinical findings and examination, and laboratory and instrumental tests, including pulmonary function tests, lung histopathology, and HRCT (without LUS findings).The final clinical diagnosis of ILD was 55 in 66 patients with suspected ILD. HRCT was positive in 55 patients, whereas LUS detected ILD in 51 patients. Four patients with negative LUS findings were positive on HRCT. The results showed 93% sensitivity, 73% specificity, 3.40 PLR, 0.10 NLR, 94% PPV, and 67% NPV for LUS, whereas 100% sensitivity, 82% specificity, 5.49 PLR, 0.01 NLR, 97% PPV, and 100% NPV for HRCT. Comparison of the 2 ROC curves revealed significant difference in the diagnostic value of the 2 methods for the diagnosis of ILD (P = .048).Our results indicated that LUS is a useful technique to identify ILD. Considering its non-radiation, portable and non-invasive advantages, LUS should be recommended as a valuable screening tool in patients with suspected ILD.

Lung ultrasound vs chest radiography in the diagnosis of children pneumonia: Systematic evidence.

BACKGROUND: The aim of this meta-analysis was to evaluate the diagnostic value of lung ultrasound (LUS) in comparison to chest radiography (CXR) in children with pneumonia. METHODS: Computer-based retrieval was performed on PubMed and EMBASE. Quality was evaluated according to the quality assessment of diagnostic accuracy studies-2, and Meta-Disc was adopted to perform meta-analysis. Heterogeneity was assessed using Q and I statistics. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs) as the primary outcomes were calculated for each index test. RESULTS: Twenty two studies with a total of 2470 patients met the inclusion criteria. Our results showed that the pooled sensitivity, specificity, and DOR for children with pneumonia diagnosed by LUS were 0.95 (95% CI: 0.94 to 0.96), 0.90 (95% CI: 0.87 to 0.92), and 137.49 (95% CI: 60.21 to 313.98), respectively. The pooled sensitivity, specificity, and DOR for pediatric pneumonia diagnosed by CXR was 0.91 (95% CI: 0.90 to 0.93), 1.00 (95% CI: 0.99 to 1.00), and 369.66 (95% CI: 137.14 to 996.47), respectively. Four clinical signs, including pulmonary consolidation, positive air bronchogram, abnormal pleural line, and pleural effusion were most frequently observed using LUS in the screening of children with pneumonia. CONCLUSIONS: The available evidence suggests that LUS is a reliable, valuable, and alternative method to CXR for the diagnosis of pediatric pneumonia.

Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury.

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury (SCI). The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI (mean age 40.94 ± 14.10 years old; male:female, 7:11) and 18 healthy subjects (37.33 ± 11.79 years old; male:female, 7:11) were studied by resting state functional magnetic resonance imaging. Gray matter volume (GMV) and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex (BA1) and left primary motor cortex (BA4), and left BA1 and left somatosensory association cortex (BA5) was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17013566).

Evaluation of the asynchronization and function of the left ventricle in patients with chronic pulmonary hypertension by velocity vector imaging.

BACKGROUND: Pulmonary hypertension (PH) is a set of pathophysiological syndromes characterized by increased pulmonary artery pressure and pulmonary vascular resistance, resulting in increased right ventricular afterload. The left and right ventricles interact through hemodynamics. What impact will PH have on synchronization and function of the left ventricle (LV)? The aim of this study was to evaluate the synchronization of the left ventricular wall motion and left ventricular function in patients with varying degrees of PH using velocity vector imaging (VVI) technology. METHODS: Sixty patients with chronic PH served as the experimental group, and 20 healthy volunteers served as the control group. According to the different degrees of pulmonary artery systolic pressure, the experimental group was divided into three groups: mild, moderate, and severe PH groups. The time to peak systolic longitudinal velocity (Tvl), the peak systolic longitudinal velocity (Vsl), the peak diastolic longitudinal velocity (Vel), the peak systolic longitudinal strain (Sl), and strain rate (SRl) in 18 segments were measured in each group. RESULTS: Tvl in the control group and each group with PH was reduced from basal to apical segment, and in control group Tvl in various segments of the same wall and in different walls showed no significant difference (P > 0.05). With increase in pulmonary artery pressure, Tvl values measured showed an increasing trend in groups with PH. In groups with PH, Vsl and Vel of each wall were reduced sequentially from basal to apical segments, showing gradient change; Vsl and Vel values measured showed a decreasing trend with increase in pulmonary artery pressure, in which the differences of Vel values measured in the control group and the mild PH group were statistically significant (P < 0.01), and the differences between other groups were statistically significant (P < 0.01). In groups with PH, Sl and SRl in basal segment and the middle segment of each wall were decreased; the difference between groups was statistically significant (P < 0.01). CONCLUSIONS: Asynchronization of the LV and decreased left ventricular function were present in patients with chronic PH; VVI technology can accurately evaluate left ventricular function in patients with PH, and indicators such as Tvl, Vsl, and Vel are valuable.

Deformation of the left and right ventricular longitudinal myocardium in fetuses with umbilical cord around neck.

BACKGROUND: Umbilical cord around neck, a common obstetric complication, affects fetal hemodynamics. Does it influence fetal cardiac functions? The purpose of this study was to investigate the left and right ventricular systolic and diastolic functions of fetuses with umbilical cord around neck in the third trimester by applying velocity vector imaging (VVI). METHODS: Thirty-five cases of fetuses with umbilical cord around neck whose gestational ages from 35 to 40 weeks were selected, including 20 cases of umbilical artery ratio of the highest systolic velocity (S) to the lowest diastolic velocity (D) (S/D) < 3.0 and 15 cases of umbilical artery S/D ≥ 3.0, while 20 cases of normal fetuses of 35 - 40 gestational weeks were selected as the control group. The changes in longitudinal velocity, strain, and strain rate of fetal left and right ventricle in systole and diastole in two groups, and the changes in fetal cardiac function under the situation of umbilical cord around neck were analyzed. RESULTS: Longitudinal strain and strain rate overall of fetal left and right ventricle in systole and diastole were less in fetuses with umbilical artery S/D (3)3.0 and umbilical cord around neck than those in fetuses with umbilical artery S/D < 3.0 and those in control group (P < 0.05); there was no significant difference (P > 0.05) in longitudinal strain and strain rate overall of fetal left and right ventricle in systole and diastole between fetuses with umbilical artery S/D < 3.0 and those in control group. CONCLUSIONS: Left and right ventricular systolic and diastolic dysfunction was detected in fetuses with umbilical cord around neck and umbilical artery S/D (3)3.0. VVI could sensitively respond to cardiac function changes in fetuses with umbilical cord around neck, which provides another valuable method in the evaluation of fetal cardiac function.