Quantitative proteomics and multi-omics analysis identifies potential biomarkers and the underlying pathological molecular networks in Chinese patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS.

Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification.

BACKGROUND: Exercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise. METHODS: Male C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments. RESULTS: In both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain. CONCLUSION: The findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification.

Long Noncoding RNA PVT1 Acts as a "Sponge" to Inhibit microRNA-152 in Gastric Cancer Cells.

BACKGROUND: PVT1 was up-regulated in patients with gastric cancer (GC) and might be as a novel biomarker for predicting GC. However, the exact mechanism of PVT1 exerting functions in GC was still poorly understood. Emerging evidence suggests that long noncoding RNAs may act as endogenous microRNA (miRNA) sponges to bind to miRNAs and regulate their function. AIM: This study aimed to determine the function of PVT1 on miR-152 expression in GC cells. METHODS: The levels of PVT1 and miR-152 were determined in GC tissues by quantitative real-time PCR. The expression of miR-152 was detected in GC cells transfected with PVT1 plasmid or siPVT1. Luciferase assay was performed to verify the regulation of miR-152 to CD151 or FGF2 expression and PVT1 to miR-152 expression. The effects of PVT1 on the expression of CD151 and FGF2 were evaluated by Western blot. RESULTS: PVT1 was up-regulated in GC tissues than that in the matched normal tissues, and mRNA level of miR-152 was decreased. MiR-152 was negatively associated with PVT1 expression in GC tissues. Based on the in silico analysis, we found that PVT1 have three binding sequences for miR-152. Moreover, PVT1 might inhibit the expression of miR-152 and increased the expression of CD151 and FGF2 through regulating miR-152. PVT1 was positively associated with CD151 and FGF2 expression in GC tissues. CONCLUSIONS: PVT1 might act as a "sponge" to inhibit miR-152 in gastric cancer cells. PVT1 is a promising molecular target to improve the diagnosis and therapy of GC.

[Research advances in circadian rhythm of epileptic seizures].

The time phase of epileptic seizures has attracted more and more attention. Epileptic seizures have their own circadian rhythm. The same type of epilepsy has different seizure frequencies in different time periods and states (such as sleeping/awakening state and natural day/night cycle). The circadian rhythm of epileptic seizures has complex molecular and endocrine mechanisms, and currently there are several hypotheses. Clarification of the circadian rhythm of epileptic seizures and prevention and administration according to such circadian rhythm can effectively control seizures and reduce the adverse effects of drugs. The research on the circadian rhythm of epileptic seizures provides a new idea for the treatment of epilepsy.

[The Role of FGF21 in Regulating Lipid and Glucose Metabolism].

Fibroblast growth factor 21 (FGF21), a member of fibroblast growth factor superfamily has received extensive attention for its positive effect on metabolism. Many tissues are target of FGF21 action. The effect of FGF21 on improving lipid and glucose metabolism has been proved. It also suggests that FGF21 plays a conspicuous role in a state of prolonged fasting and starvation. This article will review the role of FGF21 in regulating lipid and glucose metabolism and discuss the involved cellular and molecular mechanisms.

A silver catalyst with a high-energy surface prepared by plasma spraying for the hydrogen evolution reaction.

A self-supported silver electrode was prepared by plasma spraying and used for catalysing the hydrogen evolution reaction. Thanks to the non-equilibrium synthetic conditions, the silver catalyst exposes high-energy (200) crystal planes, which enhance the adsorption of hydrogen and improve the intrinsic catalytic activity. As a result, the silver catalyst delivers an overpotential of 349 mV at 10 mA cm-2, which was much lower than those of Ag foil (742 mV) and commercial Ag powder (657 mV). This work provides a new idea of preparing active electrocatalysts by traditional processes.

Preoperative evaluation of iliac blood vessels for first kidney transplant recipients: Combination of conventional and contrast-enhanced ultrasonography.

OBJECTIVE: To assess iliac blood vessels using conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) before kidney transplantation (KT) and determine whether US findings related to post-transplant outcomes. METHODS: A total of 119 patients received US and CEUS before KT waiting-list acceptance. The preoperative iliac blood hemodynamics and vascular conditions were evaluated. The operative strategy and follow-up outcomes were recorded. Logistic regression and correlation analysis were used. The accuracy in determining the patency of iliac blood vessels was calculated before and after the injection of contrast materials. RESULTS: CEUS can help to significantly improve the visualization of the internal iliac artery, but there was no significant correlation with post-transplant outcomes. In terms of accuracy, there were significant differences in determining the patency of internal iliac arteries between conventional US and CEUS (60.5% and 100%, p < 0.001). The surgical strategy of one patient was regulated and two patients were excluded from KT according to US findings. CONCLUSIONS: Compared with conventional US, CEUS helps to improve the visualization of the internal iliac artery. Conventional US and CEUS have the potential to serve as effective methods to evaluate anatomy and hemodynamics of iliac vessels and have a potential value while defining clinical algorithms in surgery decision-making.

Enhanced Synergetic Catalytic Effect of Mo2C/NCNTs@Co Heterostructures in Dye-Sensitized Solar Cells: Fine-Tuned Energy Level Alignment and Efficient Charge Transfer Behavior.

A highly efficient and stable electrocatalyst with the novel heterostructure of Co-embedded and N-doped carbon nanotubes supported Mo2C nanoparticles (Mo2C/NCNTs@Co) is creatively constructed by adopting the one-step metal catalyzed carbonization-nitridation strategy. Systematic characterizations and density functional theory (DFT) calculations reveal the advanced structural and electronic properties of Mo2C/NCNTs@Co heterostructure, in which the Co-embedded and N-doped CNTs with tunable diameters present electron-donating effect and the work function is correspondingly regulated from 4.91 to 4.52 eV, and the size-controlled Mo2C nanoparticles exhibit Pt-like 4d electronic structure and the well matched work function (4.85 eV) with I-/I3- redox couples (4.90 eV). As a result, the conductive NCNTs@Co substrate with fine-tuned energy level alignment accelerates the electron transportation and the electron migration from NCNTs@Co to Mo2C, and the active Mo2C shows high affinity for I3- adsorption and high charge transfer ability for I3- reduction, which reach a decent synergetic catalytic effect in Mo2C/NCNTs@Co heterostructure. The DSSC with Mo2C/NCNTs@Co CE achieves a high photoelectric conversion efficiency of 8.82% and exceptional electrochemical stability with a residual efficiency of 7.95% after continuous illumination of 200 h, better than Pt-based cell. Moreover, the synergistic catalytic mechanism toward I3- reduction is comprehensively studied on the basis of structure-activity correlation and DFT calculations. The advanced heterostructure engineering and electronic modulation provide a new design principle to develop the efficient, stable, and economic hybrid catalysts in relevant electrocatalytic fields.

Prediction of Tubulointerstitial Injury in Chronic Kidney Disease Using a Non-Invasive Model: Combination of Renal Sonography and Laboratory Biomarkers.

The goal of the study described here was to evaluate the degree of tubulointerstitial injury in patients with chronic kidney disease (CKD) using a more accurate model that combines renal sonographic parameters and laboratory biomarkers. A total of 308 patients were enrolled. The study protocol included conventional ultrasound, contrast-enhanced ultrasonography and renal biopsy. CKD patients were divided into normal and mild (≤25%), moderate (26%-50%) and severe (>50%) tubulointerstitial injury groups. We created a model comprising peak intensity, time to peak, urinary retinol-binding protein and ß2-microglobulin that could discriminate severe (>50%) tubulointerstitial injury. The area under the receiver operating characteristic curve of this model was 0.832, which had better accuracy than other individual indexes, and the sensitivity and specificity were 74.2% and 82.8%, respectively. Therefore, this model may be used to evaluate the severity of tubulointerstitial injury and may have the potential to serve as an effective auxiliary method to help nephrologists evaluate patients with CKD.

Quantitative parameters of contrast-enhanced ultrasonography for assessment of renal pathology: A preliminary study in chronic kidney disease.

OBJECTIVE: To assess the severity of renal pathology in patients with chronic kidney disease (CKD) using contrast-enhanced ultrasonography (US). METHODS: 275 patients with CKD who were proven by renal biopsy and 30 healthy adults were examined using conventional US and contrast-enhanced US. Ultrasonic parameters included renal length, cortical thickness, rise time (RT), peak intensity (PI), area under the time-intensity curve (AUC), wash-in slope (WIS) and time to peak (TTP). Based on pathological scores, CKD patients were classified into mild, and moderate to severe CKD groups. The logistic regression analysis and receiver operating characteristic (ROC) curves were used. RESULTS: PI and AUC differed significantly among the controls, mild and moderate to severe CKD groups (P < 0.05). There was significant difference in PI among the different pathology types (P < 0.05). The multivariate logistic regression analysis showed that PI was associated independently with the severity of renal pathology in patients with CKD (P < 0.05). PI less than 13.87 dB had a certain diagnostic ability, and the sensitivity and specificity were 72.5% and 64.0%, respectively. CONCLUSIONS: Contrast-enhanced US may be useful for noninvasive assessment of the severity of renal pathology. PI may be potentially valuable for guiding therapy and follow-up in patients with CKD.

The utility and limitations of contrast-enhanced transrectal ultrasound scanning for the detection of prostate cancer in different area of prostate.

OBJECTIVE: To evaluate the ability of contrast-enhanced transrectal ultrasound (CETRUS) scanning for prostate cancer detection in different area, compared with conventional transrectal ultrasound (TRUS). METHODS: 228 patients underwent TRUS-guided prostate biopsy after examinations of TRUS and CETRUS scanning. Cancer detection between CETRUS and TRUS were compared by patient and by site in different areas (right, left; base, mid-gland, apex). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance of CETRUS. RESULTS: 89 patients were malignant and 48 patients were significant cancer. Compared with TRUS, CETRUS could increase the detection rates of overall and significant cancer (P = 0.008; P = 0.031). CETRUS had higher sensitivity, specificity (except right lobe), accuracy, positive predictive value (PPV) and negative predictive value (NPV) in total, right and left lobe (P < 0.05). The sensitivity were greater for CETRUS in all areas except left base and right apex (P < 0.05). The accuracy were greater for CETRUS in all areas except left mid-gland and right apex (P < 0.05). ROC analysis showed CETRUS totally got the AUC of 0.816. The AUC was higher in left lobe than right lobe (0.837 vs. 0.793). It was most accurate at the base (0.833), then mid-gland (0.826), and lowest in apex (0.772). CONCLUSIONS: CETRUS had a significant advantage over conventional TRUS for prostate cancer detection in different areas. CETRUS much more easily missed the cancer in apex, we must focus more on apex and may add other imaging modalities to improve the visualization and detection of prostate cancer.

Long-term moderate exercise enhances specific proteins that constitute neurotrophin signaling pathway: A TMT-based quantitative proteomic analysis of rat plasma.

Physical exercise has been reported to increase neurotrophin in brain tissues as hippocampus as well as increased neurotrophic level peripherally in blood plasma and might have an effect on/or affect molecular processes of energy metabolism (and homeostasis). In this study, using quantitative proteomic analysis, we obtained a plasma protein profile from the rat with long-term moderate exercise. A total of 752 proteins were identified in the plasma. Among them, 54 proteins were significant up-regulated and 47 proteins were down-regulated in the plasma of exercise group compared with the control group. Bioinformatic analyses showed that these altered proteins are widely involved in multiple biological processes, molecular functions and cellular components, which connect with 11 signaling pathways. Interestingly, 5 up-regulated proteins Rap1b, PTPN11, ARHGDIA, Cdc42 and YWHAE, confirmed by Western blots, are involved in the neurotrophin signaling pathway which shows the lowest P value among the identified pathways. Further analyses showed that the 5 neurotrophin-signaling-pathway-related proteins participate in two important protein-protein interaction networks associated to cell survival and apoptosis, axonal development, synapse formation and plasticity. This study provides an exercise-induced plasma protein profile, suggesting that long-term exercise enhances the proteins involved in neurotrophin signaling pathway which may contribute to health benefit. SIGNIFICANCE: Physical activity contributes to myriad benefits on body health across the lifespan. The changes in plasma proteins after chronic moderate exercise may be used as biomarkers for health and may also play important roles in increase of cardiovascular fitness, enhancement of immune competence, prevention of obesity, decrease of risk for neurological disorders, cancer, stroke, diabetes and other metabolic disorders. Using a TMT-based proteomic method, this study identified 101 altered proteins in the plasma of rats after long-term moderate treadmill running, which may provide novel biomarkers for further investigation of the underlying mechanism of physical exercise. We confirmed that exercise enhances 5 proteins of the neurotrophin signaling pathway that may contribute to health benefits.