Search

Bladder cancer (BCa) has a high incidence and recurrence rate worldwide. So far, there is no noninvasive detection of BCa therapy and prognosis based on urine multi-omics. Therefore, it is necessary to explore noninvasive predictive models and novel treatment modalities for BCa.First, we performed protein analysis of urine from five BCa patients and five healthy individuals using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Combining multi-omics data to mine particular and sensitive molecules to predict BCa prognosis. Second, urine proteomics data were combined with TCGA transcriptome data to select differential genes that were specifically highly expressed in urine and tissues. Further, the Lasso equation was used to screen specific molecules to construct a noninvasive prediction model of BCa. Finally, natural compounds of specific molecules were selected by combined network pharmacology and molecular docking to complete molecular structure docking.A noninvasive predictive model was constructed using PSMB5, P4HB, S100A16, GET3, CNP, TFRC, DCXR, and MPZL1, specific molecules screened by multi-omics, and clinical features, which had good predictive value at 1, 3, and 5 years of prediction. High expression of these target genes suggests a poor prognosis in patients with BCa, and they were mainly involved in cell adhesion molecules and the IGF pathway. In addition, the corresponding drugs and natural compounds were selected by network pharmacology, and the molecular structure 7NHT of PSMB5 was found to be well docked to Ellagic acid, a natural compound in Hetaoren that we found. The 3D structure 6I7S of P4HB was able to bind to Stigmasterol in Shanzha stably, and the structure 6WRV of TFRC as an iron transport carrier was also able to bind to Stigmasterol in Shanzha stably. The structures 1WOJ, 3D3W, and 6IGW of CNP, DCXR, and MPZL1 can also play an important role in combination with the natural compounds (S)-Stylopine, Kryptoxanthin, and Sitosterol in Maqianzi, Yumixu, and Laoguancao.The noninvasive prediction model based on urinomics had excellent potential in predicting the prognosis of patients with BCa. The multi-omics screening of specific molecules combined with pharmacology and compound molecular docking can promote the research and development of novel drugs.

Annexin-A6 (ANXA6), a Ca2+-dependent membrane binding protein, is the largest of all conserved annexin families and highly expressed in the plasma membrane and endosomal compartments. As a multifunctional scaffold protein, ANXA6 can interact with phospholipid membranes and various signaling proteins. These properties enable ANXA6 to participate in signal transduction, cholesterol homeostasis, intracellular/extracellular membrane transport, and repair of membrane domains, etc. Many studies have demonstrated that the expression of ANXA6 is consistently altered during tumor formation and progression. ANXA6 is currently known to mediate different patterns of tumor progression in different cancer types through multiple cancer-type specific mechanisms. ANXA6 is a potentially valuable marker in the diagnosis, progression, and treatment strategy of various cancers. This review mainly summarizes recent findings on the mechanism of tumor formation, development, and drug resistance of ANXA6. The contents reviewed herein may expand researchers’ understanding of ANXA6 and contribute to developing ANXA6-based diagnostic and therapeutic strategies.

We report a novel method to synthesize bulk grain-size gradient polycrystalline Ni by AGG. By periodical sintering in the large volume press (LVP), AGG repeatedly occurs, resulting in exceptionally large grains on the sample surface, but the inner grains are still small. The formation of grain-size gradient profile is attributed to the uneven plastic deformation caused by compression in the LVP. Besides, the gradient structure can be achievable with uniformity by employing tungsten with a high shear modulus into the sample assembly. This work would guide us to design bulk heterogeneous gradient nanostructured materials with both excellent strength and ductility. The uniform grained gradient structure obtained with the improved LVP assembly. (a) The improved LVP assembly with W tablet used between Ni sample and outer Mo-capsule; (b) Inverse pole figure mapping characterization of uniform grain-size gradient structure comprised of smaller grains.

Under high dynamic conditions, a robust tracking loop is essential for accuracy positioning with the global position system. In previous studies, the extended Kalman filter (EKF)-based tracking loop technology has been proven better than the traditional tracking loop technology under high dynamic conditions. However, the performance of EKF may degrade because under high dynamic conditions, the statistics of measurement noise may change with time. In order to improve the robustness of the tracking loop under high dynamic conditions, the variational Bayesian adaptive cubature Kalman filter (VBACKF) algorithm with different types of measurement noise variances is proposed and used to track the carrier and code in this study. In the proposed algorithm, the measurement noise is considered as random variables and dynamically estimated by variational Bayesian theory. We take into consideration the two-measurement model with measurements in-phase and quadra-phase prompt (IP and QP), and the six-measurement model with measurements in-phase and quadra-phase prompt, early and late (IP, QP, IE, QE, IL and QL), and compare the proposed method with the EKF- and CKF-based tracking loops. The analytical and simulation results show that the VBACKF-based tracking loop performs better than both the EKF- and CKF-based tracking loops. Furthermore, the influence on the tracking loop of the different numbers of measurements used in the measurement model is also investigated. The results show that the phase, code and frequency tracking performances of EKF-, CKF- and VBACKF-based six measurements outperform those of the corresponding filter-based two measurements under dynamic conditions.

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is an enzyme that oxidizes acetaldehyde into acetic acid during alcohol metabolism. Many studies indicate that the rs671 GG genotype in the ALDH2 gene may play a critical role in increasing the risk of essential hypertension (EH) associated with alcohol consumption, which predominantly occurs in men. However, the literature is inconclusive in this regard. This meta-analysis aims to derive a more precise estimation of the relationship between the rs671 polymorphism and EH for both male and female drinkers and nondrinkers. Ten cohort and case-control studies were included in the analysis with a total of 12,161 subjects; 7,062 patients and 5,099 healthy controls. Our results show that the rs671 GG genotype was associated with an increased risk of EH compared with the AG+AA genotype (OR = 1.27, 95 % CI = 1.17–1.37, p

Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of death and disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and no therapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potential therapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in the organization of actin cytoskeleton, have become attractive targets for the treatment of strokes. In this study, in vitro enzyme-based assays revealed that a new compound (FPND) with a novel scaffold identified by docking-based virtual screening could inhibit ROCK1 specifically at low micromolar concentration. Molecular modeling showed that FPND preferentially interacted with ROCK1, and the difference between the binding affinity of FPND toward ROCK1 and ROCK2 primarily resulted from non-polar contributions. Furthermore, FPND significantly prevented statin-induced cerebral hemorrhage in a zebrafish model. In addition, in vitro studies using the xCELLigence RTCA system, immunofluorescence and western blotting revealed that FPND prevented statin-induced cerebral hemorrhage by enhancing endothelial cell–cell junctions through inhibiting the ROCK-mediated VE-cadherin signaling pathway. As indicated by the extremely low toxicity of FPND against mice, it is safe and can potentially prevent vascular integrity loss-related diseases, such as hemorrhagic stroke.

The oxidation behavior of CeFe4Sb12 compound in air was studied in this work. x-Ray diffractometry, scanning electron microscopy observation, and activation energy calculation suggest that CeFe4Sb12 is very easily oxidized at elevated temperature. The reason for the weak resistance to oxidation is mainly due to the unstable “FeSb3” structure and the high Ce filling fraction in the skutterudite voids. At elevated temperature, Ce fillers which have high oxygen affinity firstly react with oxygen. This process proceeds accompanied by decomposition of “Fe4Sb12” into FeSb2 and Sb, which in turn accelerates the oxidation rate. The Ce fillers in CeFe4Sb12 provide a short path for rapid interdiffusion of oxygen, which leads to fast growth of the oxide layer, with thickness of about 200 μm at 900 K after only 1 h exposure in air. This result suggests that appropriate protection from oxidation is necessary for real applications of CeFe4Sb12.

This study investigated the mechanism of the cytotoxic effect of emodin, an active anthraquinone, on human lung adenocarcinoma A549 cells. In vitro growth inhibition and suppression on colony forming were used to evaluate the effects of emodin on A549 cells. Emodin's ability in changing the expressions of apoptosis-related genes was studied by real-time RT-PCR. Emodin could significantly inhibit the growth of A549 cells with IC50 = 16.85 μg/ml (~60 μM). It also concentration dependently inhibited the colony-forming ability of A549 cells with IC50 = 7.60 μg/ml (~30 μM). Hallmarks of apoptosis, such as single-strand DNA breakage and DNA fragmentation, were observed in A549 cells treated with emodin. Emodin (72 h) treatment could up-regulate the gene expression of FASL (p < 0.05) and down-regulate the gene expression of C-MYC (p < 0.01), but induce no significant changes in the gene expressions of MCL1, GAPDH, BAX and CCND1. These results suggest that emodin could induce growth inhibition and apoptosis in A549 cells through modifying the extrinsic apoptotic pathways and the induction of cell cycle arrest.

The anticancer effects of traditional Chinese medicine (TCM) have attracted the attention of the public vis-à-vis existing cancer therapies with various side effects. Lycium barbarum fruit, commonly known as Gou Qi Zi in China, is a potential anticancer agent/adjuvant. Its major active ingredients, L. barbarum polysaccharides (LBP), scopoletin and 2-O-β-D-glucopyranosyl-L-ascorbic acid (AA-2βG), are found to have apoptotic and antiproliferative effects on cancer cell lines. Moreover, LBP also contributes to body's immunomodulatory effects and enhances effects of other cancer therapies. It is not known whether there are any undesirable effects. Further studies on its pharmacological mechanisms and toxicology could facilitate a safe usage of this TCM herb.

Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock.

Background Panax notoginseng is commonly used for the treatment of cardiovascular diseases in China. The present study investigates the effects of three different saponin fractions (ie total saponins, PNS; protopanaxadiol-type saponin, PDS; and protopanaxatriol-type saponin, PTS) and two major individual ingredients (ie ginsenoside Rg1 and Rb1) from P. notoginseng on the endothelial inflammatory response in vitro and in vivo. Methods Recombinant human tumor necrosis factor-α (TNF-α) was added to the culture medium of human coronary artery endothelial cells (HCAECs) to induce an inflammatory response. A cell adhesion assay was used to determine the effect of the P. notoginseng saponin fractions on endothelial-monocyte interaction. The cell adhesion molecule (CAMs) expression, including ICAM-1 and VCAM-1, in the protein level on the surface of endothelial cells were measured by cellular ELISA. CAMs expression in mRNA level was also assayed by qRT-PCR in the HCAECs and the aorta of rat fed with high cholesterol diet (HCD). Western blotting was used to detect effect of the saponin fractions on CAMs protein expression in HCAECs. In addition, nuclear translocation of p65, a surrogate marker for NF-κB activation, was measured by immunostaining. Results Three saponin fractions and two individual ginsenosides exhibited the inhibitory effects on monocyte adhesion on TNF-α-activated HCAECs and expression of ICAM-1 and VCAM-1 at both mRNA and protein levels in vitro. The saponin fractions exhibited a similar trend of the inhibitory effects on the mRNA expression of CAMs in the aorta of HCD-fed rat in vivo. These inhibitory effect of saponin fractions maybe attribute partially to the suppression of the TNF-α-induced NF-κB activation. Conclusion Our data demonstrate that saponin fractions (ie PNS, PDS and PTS) and major individual ginsenosides (ie Rg1 and Rb1) have potential anti-atherogenic effects. Among the tested saponin fractions, PDS is the most potent saponin fraction against TNF-α-induced monocyte adhesion as well as the expression of adhesion molecules in vitro and in vivo.