Extracellular Vesicles from Neural Stem Cells Carry microRNA-16-5p to Reduce Corticosterone-induced Neuronal Injury in Depression Rats.

OBJECTIVE: Depression is a common mental illness. Neural stem cell-derived extracellular vesicles (NSC-EVs) are involved in repairing neuronal injury. We estimated the mechanism of miR-16-5p in depression rats. METHODS: EVs were extracted from NSCs. The depression rat model was established by corticosterone (CORT) induction and treated with NSC-EVs. The depression behavioral/pathological changes in rats were assessed using forced swimming test, open field test, sucrose consumption test and western blotting. The neuronal apoptosis in hippocampal tissue were detected. CORT-induced PC12 cell model was established. EV uptake by PC12 cells was measured and PC12 cell apoptosis was detected. The downstream targets of miR-16-5p were predicted and verified. The expressions of miR-16-5p and MYB in rats, PC12 cells, and EVs were measured. Functional rescue experiments were conducted to verify the role of miR-16-5p and MYB in PC12 cell apoptosis. RESULTS: CORT induction increased neuronal apoptosis in hippocampal tissue and induced depression-like behaviors in rats, while NSC-EV treatment improved depression-like behaviors and apoptosis in rats. In PC12 cells, NSC-EVs decreased CORT-induced PC12 cell apoptosis. NSC-EVs carried miR-16-5p into PC12 cells. miR-16-5p knockdown in EVs partially reversed the inhibitory effects of NSC-EVs on CORT-induced PC12 cell apoptosis. miR-16-5p targeted to inhibit MYB to repress CORT-induced PC12 cell apoptosis. In vivo experiments further verified that NSC-EVs reduced neuronal injury in CORT-induced depression rats via the miR-16-5p/MYB axis. CONCLUSION: NSC-EVs-mediated alleviation on neuronal injury by carrying miR-16-5p to target MYB was highly likely one of the mechanisms by which NSC-EVs mediated miR-16-5p in neuroprotection of depression rats.

Influence of Health Education Based on IMB on Prognosis and Self-Management Behavior of Patients with Chronic Heart Failure.

As the contemporary society is increasingly entering an aging society, heart failure, as a common disease in the elderly population, has an increasing impact on people. The common one is mainly chronic heart failure. Coupled with the influence of various complications, such as hypostatic pneumonia and venous thrombosis, the mortality and hospital admission rates of patients are very high. Moreover, the current technology is not very effective for the prevention and treatment of chronic heart failure. The per capita consumption level of ordinary people in China is low, and it is not suitable to promote high-cost treatment programs. Based on this, this paper proposes the intervention management of mental failure patients under the intervention of health education based on IMB, in order to explore the impact of the intervention of health education on patients. The research in this paper selected 112 patients with chronic heart failure who were admitted to the cardiovascular ward of a city public hospital in 2017 and divided the patients into two groups. One group received health education intervention, which was the intervention group. The other group was the control group. The control group was given routine education and nursing. The experimental results of this paper show that the satisfaction of the intervention group is higher, accounting for 85.3%, and the satisfaction of the control group is lower than that of the intervention group, about 67.9%. Dissatisfaction with health education and the probability of short-term readmission were higher than those in the intervention group.

Role of contrast-enhanced ultrasonography in MR-guided focused ultrasound ablation on uterus fibroids: lesion selection and assessment of ablative effects.

OBJECTIVES: To determine whether contrast-enhanced ultrasonography (CEUS) can be used for selecting lesions and assessing the ablative effects of MRgFUS ablation on uterus fibroids, compared with MR imaging. METHODS: This retrospective study was approved by the institutional review board of our hospital. From April 2018 to November 2019, a total of 44 symptomatic fibroids in 38 patients who underwent MRgFUS ablation were included. The association between pre-ablation characteristics on CEUS/MR imaging and the non-perfusion volume (NPV) after ablation was analyzed using multivariable linear regression analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve values was compared between the CEUS and MR imaging regression models. NPV after ablation was compared between CEUS and enhanced MR imaging. RESULTS: On CEUS, entangled branch vessels, fast-in, and fast-out patterns were significantly associated with NPV, with an AUC of 0.95 (95% CI; 0.88, 1.00). On MR imaging, hyper-intensity on T2-weighted images (T2WI), hyper-intense ring-like signal on T2WI images, and hyper-enhancement on contrast-enhanced T1WI images were correlated with NPV, with an AUC of 0.86 (95% CI; 0.70, 1.00). After ablation, no differences in NPV were noted between contrast-enhanced T1WI (84.13 ± 75.42 cm3) and CEUS (80.22 ± 76.49 cm3). CONCLUSIONS: Some pre-ablation characteristics of uterine fibroids on CEUS were associated with NPV after MRgFUS. CEUS may contribute to the evaluation of ablative outcomes and patient selection, similar to MR imaging. KEY POINTS: • Contrast-enhanced ultrasonography (CEUS) is effective for selecting the appropriate uterine fibroids before MR-guided focused ultrasound (MRgFUS) ablation and evaluating non-perfusion volumes (NPV) after ablation, as a potential alternative to MR imaging. • Before ablation, entangled branch vessels, fast-in, and fast-out patterns on CEUS were significantly associated with NPV after MRgFUS. • No significant differences in NPV were detected between contrast-enhanced T1WI and CEUS after ablation.

Metabolomics in renal cell carcinoma: From biomarker identification to pathomechanism insights.

Renal cell carcinoma (RCC) is a frequently diagnosed cancer with high prevalence, which is inversely associated with survival benefit. Although myriad studies have shed light on disease causality, unfortunately, thus far, RCC diagnosis is faced with numerous obstacles partly due to the insufficient knowledge of effective biomarkers, hinting deeper mechanistic understanding are urgently needed. Metabolites are recognized as final proxies for gene-environment interactions and physiological homeostasis as they reflect dynamic processes that are ongoing or have been taken place, and metabolomics may therefore offer a far more productive and cost-effective route to disease discovery, particularly within the arena for new biomarker identification. In this review, we primarily expatiate recent advances in metabolomics that may be amenable to novel biomarkers or therapeutic targets for RCC, which may expand our armaments to win more bettles against RCC.

Redox signaling and Alzheimer's disease: from pathomechanism insights to biomarker discovery and therapy strategy.

ABSTRACT: Aging and average life expectancy have been increasing at a rapid rate, while there is an exponential risk to suffer from brain-related frailties and neurodegenerative diseases as the population ages. Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide with a projected expectation to blossom into the major challenge in elders and the cases are forecasted to increase about 3-fold in the next 40 years. Considering the etiological factors of AD are too complex to be completely understood, there is almost no effective cure to date, suggesting deeper pathomechanism insights are urgently needed. Metabolites are able to reflect the dynamic processes that are in progress or have happened, and metabolomic may therefore provide a more cost-effective and productive route to disease intervention, especially in the arena for pathomechanism exploration and new biomarker identification. In this review, we primarily focused on how redox signaling was involved in AD-related pathologies and the association between redox signaling and altered metabolic pathways. Moreover, we also expatiated the main redox signaling-associated mechanisms and their cross-talk that may be amenable to mechanism-based therapies. Five natural products with promising efficacy on AD inhibition and the benefit of AD intervention on its complications were highlighted as well.

Correction: LRP6 promotes invasion and metastasis of colorectal cancer through cytoskeleton dynamics.

[This corrects the article DOI: 10.18632/oncotarget.22759.].

Identification and biochemical characterization of the glutathione reductase family from Populus trichocarpa.

Glutathione reductase (GR; EC 1.6.4.2) is a key NADPH-dependent flavo-protein oxidoreductase which can catalyze the oxidized glutathione (GSSG) to reduced glutathione (GSH) to protect plant cells from oxidative damage induced by Reactive oxygen species (ROS) burst. To investigate the biochemical characteristics and functional divergence of Populus GR family, three GR genes (PtGR1.1/1.2/2) were cloned from Populus trichocarpa and their biochemical characteristics were analyzed in this study. All the three genes were expressed in root, stem, leaf and bud, and the expression of PtGR genes were general upregulated under salicylic acid and alamethicin treatment. PtGR1.1 and PtGR1.2 were localized in cytoplasm, while PtGR2 was in chloroplast. The three PtGR proteins showed different enzymatic activities, apparent kinetic characteristic and thermal stability profiles. However, they have similar bivalent metal ions (Cu2+, Cd2+, Zn2+ and Pb2+) sensitivity and optimum pH profiles. Our study sheds light on a comprehensive information of glutathione reductase family in P. trichocarpa, and proved PtGR genes play critical roles when suffering different stresses.

[Design of moxibustion device for experimental rabbits].

An experimental device is designed to solve the problem of fixing rabbits and providing moxibustion treatment at the same time. The device includes a rabbit fixing box and a moxibustion shelf. The rabbit fixing box and the moxibustion shelf are detachable, and could be used for moxibustion at the chest-back and abdomen of rabbits. A moxibustion device is placed on the moxibustion shelf. The moxibustion device can be moved forward, backward, leftward, rightward, upward and downward on the moxibustion shelf. It meets the requirements of moxibustion at multiple meridians or acupoints on the chest-back and abdomen at the same time. The moxibustion device is equipped with moxa cone or stick, which not only ensures the full burning of moxa, but also prevents the falling of moxa from hurting rabbits. In conclusion, the device has novel and unique structure, is safe and reliable, and easy to operate. It is an innovation in the experimental device of moxibustion, which could promote the animal experiment of moxibustion.

Identification and Differentiation of Polygonum multiflorum Radix and Polygoni multiflori Radix Preaparata through the Quantitative Analysis of Multicomponents by the Single-Marker Method.

The quantitative analysis of multicomponents by the single-marker (QAMS) method was established and the relationship between F value (the ratio of the sum of the contents of emodin-8-O-ß-D-glucopyranoside and physcion-8-O-ß-D-glucopyranoside to the sum of the contents of emodin and physcion) and the steaming time was found to identify and differentiate Polygonum multiflorum Radix and its processed product. Emodin was considered as the control substance, and the correction factors of physcion, emodin-8-O-ß-D-glucopyranoside, and physcion-8-O-ß-D-glucopyranoside were computed. In addition, the contents of the four components were determined. When the F value is greater than or equal to 1.0, the sample was identified as Polygonum multiflorum Radix, and if the F value was between 0.6 and 1.0, the sample of Polygoni multiflori Radix Preaparata was processed incompletely. The F value of the qualified Radix Polygonum multiflorum should be no more than 0.6. However, the influence of different sample injection volumes and the chromatographic columns and instruments used on the durability of the correction factors and RSD ≤3% hindered accurate identification; therefore, a QAMS method using an external standard value with methodological verification was developed. We redefined the "Polygonum multiflorum rules." The method using "Polygonum multiflorum rules" revised after optimization of the determination results was used, as it was accurate and led to convenient operation and low inspection costs, and moreover, the method could differentiate Polygoni multiflori Radix Preaparata and Polygonum multiflorum Radix medicinal samples and precisely identify samples that were different from the completely processed product Polygoni multiflori Radix Preaparata.

Analysis of the Effect of 60Co-γ Irradiation Sterilization Technology on the Chemical Composition of Saffron Using UPLC and UPLC/Q-TOF-MS.

To evaluate the effect of 60Co-γ irradiation sterilization technology on the chemical composition of saffron, we collected 10 batches of saffron samples and treated them with different irradiation doses. UPLC characteristic chromatogram showed that there was no significant effect of irradiation on 13 common peak areas. The results of cluster analysis and principal component analysis showed that there were no differences in the chemical composition in nonirradiated and irradiated samples. UPLC/Q-TOF-MS identified 40 characteristic components of saffron, and the results showed that all of these were detected in the saffron samples both with and without irradiation. Irradiation doses at or below 10 kGy had no significant effect on the chemical components of saffron. This provides a sound basis for the use of 60Co-γ ray irradiation sterilization technology during the preparation of original powder saffron as a medicinal herb, for the effective destruction of mycotoxin contamination.

Effects of silibinin-loaded thermosensitive liposome-microbubble complex on inhibiting rabbit liver VX2 tumors in sub-hyperthermia fields.

In the present study, the effects of silibinin-loaded thermosensitive liposome-microbubble complex (STLMC) on rabbit liver VX2 tumors in sub-hyperthermia fields were investigated using two-dimensional ultrasonography (2D US), contrast-enhanced US (CEUS), hematoxylin and eosin (H&E) staining, immunohistochemistry and ultrastructure observation. 50 rabbits with VX2 liver tumors were divided into five groups: Sub-hyperthermia microwave ablation group (SHM), STLMC injection group (STLMC), SHM ablation plus STLMC injection group (SHM + STLMC), microbubble injection group and blank control group without any treatment. Rabbits in each group were examined using 2D US and CEUS in order to evaluate the tumor volume and diameter before treatment and at day 7 and 21 after treatment. Morphology, expression of CD163 and CD206, and ultrastructure of the tumors were assessed. The average post-treatment volume of tumors in group SHM + STLMC was 1.17±0.88 cm3 at day 7 and 2.15±0.96 cm3 at day 21, which was significantly decreased compared with all other groups (P<0.05). H&E staining indicated that the number of disordered macrophages in the SHM + STLMC group significantly increased compared with the other groups (P<0.05). Immunohistochemical results demonstrated that in the SHM + STLMC, the expression of CD163 and CD206 significantly decreased compared with all other groups (P<0.05). These results suggested that STLMC has a potential function in preventing tumor growth, which may be due to its inhibitory effect on tumor-associated macrophages in the tumor microenvironment.

LRP6 promotes invasion and metastasis of colorectal cancer through cytoskeleton dynamics.

Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis. In addition, phosphorylated LRP6 was positively correlated with nuclear accumulation of ß-catenin. Overexpression or activation of LRP6 could activate Wnt signaling and promote tumor cell migration in vitro. The activation of LRP6 could induce microtubule dynamics and actin remodeling, probably through regulation of microtubule-associated protein 1B (MAP1B), microtubule actin cross-linking factor 1 (MACF1) and Rho GTPase--RhoA and Rac1. The investigation suggests that LRP6 may be a potential prognostic marker and therapeutic target in the progression of colorectal cancers.

Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.

Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.

GSK-3ß-regulated N-acetyltransferase 10 is involved in colorectal cancer invasion.

PURPOSE: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution. EXPERIMENTAL DESIGN: The expression and subcellular redistribution of NAT10, ß-catenin, E-cadherin, and GSK-3ß were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3ß, transfection of wild-type or kinase-inactivated GSK-3ß, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays. RESULTS: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive "leading edge" of the tumor. This correlated well with nuclear accumulation of ß-catenin (P<0.001; χ2=68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values<0.001), and was associated with a poorer prognosis (P=0.023; χ2=5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3ß. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility. CONCLUSION: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3ß activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma.

Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family.

Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families.

Girdin correlated with autophagy in invasive ductal breast carcinomas.

AIMS AND BACKGROUND: Increasing evidence claims that autophagy is essential for breast cancer progression. Girdin was found highly expressed in breast cancers. It has been reported that Girdin attenuates autophagy in HeLa cells. We explored the relationship between Girdin expression and autophagic patterns in breast cancer. METHODS AND STUDY DESIGN: In the study, Girdin expression and autophagic activity were investigated in a series of 99 invasive ductal breast carcinomas after immunohistochemical staining for the autophagy-associated proteins LC3-II and Girdin. RESULTS: The level of Girdin expression negatively correlated with LC3-II level, which represents autophagic activity (r = -0.289), and positively correlated with lymph node metastasis (r = 0.472). Girdin level was found no different in the "diffuse cytoplasmic" and "stone-like" patterns of LC3-II. CONCLUSIONS: Up-regulated autophagy was negatively associated with Girdin level. There was a significant correlation between Girdin expression and lymph nodes metastasis in invasive ductal breast carcinoma.

[Analysis of Spirulina powder by Fourier transform infrared spectroscopy and calculation of protein content].

Spirulina, Spirulina powder and dextrin standard were analyzed and identified by Infrared (IR) spectroscopy. The main components, protein (1 657 and 1 537 cm(-1)) and carbohydrate (1 069 and 1054 cm(-1)), had distinct fingerprint characteristics of IR spectra. By comparing the IR spectra of Spirulina, Spirulina powder and dextrin standard, the dominant nutrition in Spirulina powder was identified as protein and carbohydrate. The dominant accessory added in Spirulina powder was dextrin. Comparing the IR spectra of Spirulina powder from 28 different factories and figuring out the correlation provides the information about the amount of accessory. A standard curve of the ratio of absorption peak intensities to protein content was constructed to accurately determine the amount of protein in Spirulina powder.

Mechanically resilient electrospun TiC nanofibrous mats surface-decorated with Pt nanoparticles for oxygen reduction reaction with enhanced electrocatalytic activities.

Mechanically resilient mats consisting of overlaid electrospun nanofibers with self-generated TiC crystallites embedded in a carbon matrix are surface-decorated with Pt nanoparticles as a novel electrocatalytic system for oxygen reduction reaction. Electrocatalytic activities (e.g., on-set potential and current density) of Pt are substantially enhanced due to high specific surface area of the support and the synergetic effect of TiC and Pt on electrocatalysis.

The level of phosphorylated Akt predominantly reflects the expressive status of CerbB2 in invasive breast cancer.

Although some evidence has been documented on EGFR/PI3K mediation of Akt activation in breast cancers, ILK and DNA-PK have not been investigated so far. The aim of this study was to analyze the expression of phosphorylated Akt (pAkt) in breast cancer, with respect to its upstream regulators. The immunostaining of pAkt (Ser473) in 70 invasive breast cancers revealed that status of CerbB2 could play a major role in Akt phosphorylation, while ILK was also involved in the stimulated level of pAkt. The results would provide an important clue for the activation of Akt and potential targeted therapy in breast cancer.

Molecular evolution and expression divergence of the Populus polygalacturonase supergene family shed light on the evolution of increasingly complex organs in plants.

Plant polygalacturonases (PGs) are involved in cell separation processes during many stages of plant development. Investigation into the diversification of this large gene family in land plants could shed light on the evolution of structural development. We conducted whole-genome annotation, molecular evolution and gene expression analyses of PG genes in five species of land plant: Populus, Arabidopsis, rice, Selaginella and Physcomitrella. We identified 75, 44, 16 and 11 PG genes from Populus, rice, Selaginella and Physcomitrella genomes, respectively, which were divided into three classes. We inferred rapid expansion of class I PG genes in Populus, Arabidopsis and rice, while copy numbers of classes II and III PG genes were relatively conserved in all five species. Populus, Arabidopsis and rice class I PG genes were under more relaxed selection constraints than class II PG genes, while this selective pressure divergence was not observed in Selaginella and Physcomitrella PG families. In addition, class I PG genes underwent marked expression divergence in Populus, rice and Selaginella. Our results suggest that PG gene expansion occurred after the divergence of the lycophytes and euphyllophytes, and this expansion was likely paralleled by the evolution of increasingly complex organs in land plants.