Total astragalosides promote oligodendrocyte precursor cell differentiation and enhance remyelination in cuprizone-induced mice through suppression of Wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali is a traditional Chinese medicine with various pharmacological effects. Total astragalosides (TA), the main effective ingredients in Radix Astragali, exert properties including anti-oxidative stress, anti-neuroinflammation, and neuroprotection. We previously found that TA alleviated experimental autoimmune encephalomyelitis (EAE) progression, a widely used animal model of multiple sclerosis (MS). As a chronic demyelination disease, MS generally manifests myelin loss and fails to myelin regeneration. Regulation of oligodendrocyte progenitor cells (OPCs) differentiation and remyelination is the fundamental strategy for MS treatment. However, whether TA could directly promote OPCs differentiation and remyelination is still unknown. AIMS OF THE STUDY: This study was aimed to investigate pro-differentiation and myelin regeneration effects of TA on OPCs and Cuprizone (CPZ)-induced demyelination mice, an animal model of MS, and to explore mechanism underlying from regulation of OPCs differentiation and maturation. MATERIALS AND METHODS: Mice were orally given CPZ (400 mg/kg) daily for 4 weeks to induce myelin loss, and then treated with TA (25 and 50 mg/kg) daily for 1 week. Cell proliferation assay, Western blot, RT-PCR, immunocytochemistry and immunohistochemistry were performed to explore the mechanisms. The role of TA in oligodendrocyte differentiation and maturation was evaluated using MO3.13, a human oligodendrocytic hybrid cell line. RESULTS: TA was shown to mitigate behavioral impairment in CPZ-induced mice. It markedly ameliorated myelin loss and enhanced remyelination in the corpus callosum of mice, evidenced by increased expression of myelin basic protein (MBP) and the number of CC1+ newly generated oligodendrocytes (OLs). TA also enhanced the expression of MBP at both mRNA and protein levels in MO3.13 cells. In CPZ-induced mice and MO3.13 cells, TA remarkably promoted the activation of GSK3ß, repressed the phosphorylation of ß-catenin, reduced the expression of transcription factor 4 and inhibitor of DNA binding 2. The agonist of ß-catenin, SKL2001, partially abolished the pro-differentiation effect of TA in MO3.13 cells. CONCLUSIONS: Taken together, we clarified that TA could effectively enhance the differentiation and maturation of OPCs and accelerate remyelination in CPZ-induced mice through inhibition of Wnt/ß-catenin signaling pathway. This study provides new insight into the beneficial effect of TA in the treatment of MS.

Zinc-Loaded Black Phosphorus Multifunctional Nanodelivery System Combined With Photothermal Therapy Have the Potential to Treat Prostate Cancer Patients Infected With COVID-19.

Since 2019, coronavirus disease 2019 (COVID-19) has swept the world and become a new virus threatening the health of all mankind. The survey found that prostate cancer accounts for one in three male cancer patients infected with COVID-19. This undoubtedly makes prostate cancer patients face a more difficult situation. Prostate cancer is the second most harmful malignant tumor in men because of its insidious onset, easy metastasis, and easy development into castration-resistant prostate cancer even after treatment. Due to its high immunogenicity and a small number of specific infiltrating T cells with tumor-associated antigens in the tissue, it is difficult to obtain a good therapeutic effect with immune checkpoint blocking therapy alone. Therefore, in the current study, we developed a platform carrying Doxorubicin (DOX)-loaded black phosphate nanometer combined with photothermal therapy (PTT) and found this drug combination stimulated the immungentic cell death (ICD) process in PC-3 cells and DC maturation. More importantly, zinc ions have a good immunomodulatory function against infectious diseases, and can improve the killing ability of the nanosystem against prostate cancer cells. The introduction of Aptamer (Apt) enhances the targeting of the entire nanomedicine. We hope that this excellent combination will lead to effective treatment strategies for prostate cancer patients infected with COVID-19.

AGRNet: Adaptive Graph Representation Learning and Reasoning for Face Parsing.

Face parsing infers a pixel-wise label to each facial component, which has drawn much attention recently. Previous methods have shown their success in face parsing, which however overlook the correlation among facial components. As a matter of fact, the component-wise relationship is a critical clue in discriminating ambiguous pixels in facial area. To address this issue, we propose adaptive graph representation learning and reasoning over facial components, aiming to learn representative vertices that describe each component, exploit the component-wise relationship and thereby produce accurate parsing results against ambiguity. In particular, we devise an adaptive and differentiable graph abstraction method to represent the components on a graph via pixel-to-vertex projection under the initial condition of a predicted parsing map, where pixel features within a certain facial region are aggregated onto a vertex. Further, we explicitly incorporate the image edge as a prior in the model, which helps to discriminate edge and non-edge pixels during the projection, thus leading to refined parsing results along the edges. Then, our model learns and reasons over the relations among components by propagating information across vertices on the graph. Finally, the refined vertex features are projected back to pixel grids for the prediction of the final parsing map. To train our model, we propose a discriminative loss to penalize small distances between vertices in the feature space, which leads to distinct vertices with strong semantics. Experimental results show the superior performance of the proposed model on multiple face parsing datasets, along with the validation on the human parsing task to demonstrate the generalizability of our model.

Bioinformatics and experimental findings reveal the therapeutic actions and targets of pachymic acid against cystitis glandularis.

Pachymic acid (PA), a bioactive ingredient isolated from Poria cocos Wolf, is reported with potential benefits of anti-inflammatory, anti-oxidative actions. It is reasoned that PA may play the potential benefits against cystitis glandularis (CG), an inflammation of the bladder tissue. In this study, we aimed to apply the network pharmacology and molecular docking analyses to reveal concrete anti-CG targets and mechanisms of PA, and then the bioinformatic findings were verified by using clinical and animal samples. The methodological data from network pharmacology approach showed that 303 and 243 reporting targets of CG and PA, and other 31 shared targets of CG and PA were identified. Subsequently, all top targets of PA against CG were screened out, including cyclooxygenase-2, epidermal growth factor receptor, tumor antigen p53 (TP53), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) beta, proto-oncogene c-jun. Molecular docking data demonstrated that PA exerted potent bonding capacities with TNF, TP53 proteins in CG. In human study, the findings suggested that overactivated TNF-α expression and suppressed TP53 activation were detected in CG samples. In animal study, PA-treated mice showed reduced intravesical IL-1, IL-6 levels, and lactate dehydrogenase content, downregulated TNF-α and upregulated TP53 proteins in bladder samples. Taken together, our bioinformatics and experimental findings identify the key anti-CG biotargets and mechanisms of PA. More markedly, these pivotal pharmacological targets of PA against CG have been screened out and verified by using computational and experimental analyses.

Prognostic Value of Genes and Immune Infiltration in Prostate Tumor Microenvironment.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers and the fifth leading cause of cancer-related death in men. Immune responses in the tumor microenvironment are hypothesized to be related to the prognosis of PCa patients; however, no studies are available to confirm the same. In this study, we aimed to explore the potential link between these two factors and identify new biomarkers to estimate the survival rate of PCa patients. METHODS: A total of 490 cases were obtained from The Cancer Genome Atlas (TCGA) database. The gene expression data were analyzed by the ESTIMATE algorithm to evaluate the immune and stromal scores. The survival rate was calculated according to the case-specific clinical data. Enrichment analysis was performed to discover the main biological processes and signaling pathways of immune responses. We further identified and analyzed hub genes in the protein-protein interaction (PPI) network and evaluated their prognostic values. RESULTS: Immune score significantly correlated with immune cell infiltration and overall survival of PCa patients. The genes CXCR4 and GPR183, identified as hub genes in the PPI network, correlated with immune cell infiltration and prognosis of PCa patients. CONCLUSION: CXCR4 and GPR183 participate in immune cell infiltration and function in PCa patients. The immune score, as well as the expression of CXCR4 and GPR183 in prostate cancer tissues, could be potential indexes for the prognosis of prostate cancer.

Physiological and Biochemical Mechanisms Mediated by Allelochemical Isoliquiritigenin on the Growth of Lettuce Seedlings.

Isoliquiritigenin, a natural chalcone-type flavonoid, has been recognized as an allelochemical with phytotoxicity to lettuce; however, not enough attention has been paid to the mechanisms of this secondary metabolite. In this work, we investigated the physiological and biochemical mechanisms of isoliquiritigenin on lettuce seedlings. The results show that isoliquiritigenin has a concentration-dependent inhibitory effect on radicle elongation of lettuce seedlings, but no significant impact on lettuce germination. Microscopy analyses suggest that the surface morphology of lettuce radicle tips was atrophied and the intracellular tissue structure deformed at high concentrations. Isoliquiritigenin induced the overproduction of reactive oxygen species (ROS), which led to loss of cell viability in the radicle cells. In addition, malondialdehyde (a product of lipid peroxidation) and free proline levels were found to have increased, while chlorophyll content in lettuce seedlings decreased. All these changes suggest that the primary allelopathic mechanism of isoliquiritigenin by which it inhibits radicle elongation in lettuce seedlings might be due to the overproduction of ROS, which causes oxidative damage to membrane lipids and cell death.

A high Precision Time Grating Displacement Sensor Based on Temporal and Spatial Modulation of Light-Field.

A new displacement sensor with light-field modulation, named as time grating, was proposed in this study. The purpose of this study was to reduce the reliance on high-precision measurements on high-precision manufacturing. The proposed sensor uses a light source to produce an alternative light-field simultaneously for four groups of sinusoidal light transmission surfaces. Using the four orthogonally alternative light-fields as the carrier to synthesize a traveling wave signal which makes the object movement in the spatial proportion to the signal phase shift in the time, the moving displacement of the object can be measured by counting time pulses. The influence of the light-field distribution on sensor measurement error was analyzed in detail. Aimed to reduce these influences, an optimization method that used continuous cosinusoidal light transmission surfaces with spatially symmetrical distribution was proposed, and the effectiveness of this method was verified with simulations and experiments. Experimental results demonstrated that the measurement accuracy reached 0.64 µm, within the range of 500 mm, with 0.6 mm pitch. Therefore, the light-field time grating can achieve high precision measurement with a low cost and submillimeter period sensing unit.

Knockdown of lncRNA SNHG7 inhibited cell proliferation and migration in bladder cancer through activating Wnt/ß-catenin pathway.

It is identified that long non-coding RNAs (lncRNAs) play important roles in tumorigenesis. LncRNA SNHG7 has been found to be an oncogene in varieties of tumors including bladder cancer. However, its potential regulatory mechanism in bladder cancer still remains unknown. In this study, we discovered that the expression levels of SNHG7 were significantly increased in bladder cancer tissues and cell lines. Patients with high expression level of SNHG7 suffered from poor prognosis. Additionally, knockdown of SNHG7 induced declined cell viability, proliferation as well as G0/G1 cell cycle arrest. Furthermore, we found that cell migratory ability was markedly reduced after silencing SNHG7. Next, we verified that knockdown of SNHG7 reduced the protein level of ß-catenin and thus decreased the level of its downstream targets including c-myc, cyclin D1 and E-cadherin, implying that SNHG7 might impact bladder cancer via Wnt/ß-catenin pathway. Subsequently, the rescue assays performed in SNHG7 silenced T24 cells by using activator of Wnt/ß-catenin signaling elucidated that re-activation of this pathway partly restored the inhibitory effects of SNHG7 suppression on biological behaviors of T24 cells. Collectively, SNHG7 elicited carcinogenic functions in bladder cancer partially via activating Wnt/ß-catenin signaling pathway, suggesting a potential target for the treatment and prognosis of bladder cancer.

LncROR Promotes Bladder Cancer Cell Proliferation, Migration, and Epithelial-Mesenchymal Transition.

BACKGROUND: LncRNA ROR, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, the molecular biological function in bladder cancer has not been clearly elucidated. The aim of this study is to explore ROR expression levels and evaluated its function in bladder cancer. METHODS: LncRNA ROR expression levels in the 36 pairs of bladder cancer tissues (and corresponding non-tumor tissues) and bladder cancer cells were assessed by qRT-PCR. MTT assay, colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays, attachment/detachment and western blotting were performed to assess the effects of ROR on proliferation, apoptosis, migration/invasion and epithelial-to-mesenchymal (EMT) phenotypes in BC cells in vitro. ZEB1 is target of ROR. Rescue assays were performed to further confirm that ROR contributes to the progression of BC cells through targeting ZEB1. RESULTS: LncRNA ROR was up-regulated in bladder cancer tissues (compared to adjacent non-tumor tissues) and was almost overexpression in bladder cancer cells (compared with normal urothelial cell line SVHUC-1 cells). Increased lncRNA ROR expression significantly promoted tumor cells proliferation, inhibited cells apoptosis, facilitated cells metastasis and contributed to the formation of EMT phenotype. While down-regulated ROR could obviously inhibit cells proliferation, promote cells apoptosis, inhibit metastasis and reverse EMT to MET. ZEB1 was a target gene of ROR and was positive correlation with the level of ROR in cancer tissues. CONCLUSION: These results indicated that lncRNA ROR was associated with tumor progression in bladder cancer cells.

MiR-26a inhibits cell proliferation and induces apoptosis in human bladder cancer through regulating EZH2 bioactivity.

Bladder cancer is the second most common malignant tumor of the urinary tract worldwide and is associated with significant morbidity and mortality. EZH2, the enzymatic subunit of Polycomb repressive complex 2 (PRC2), is frequently overexpressed in multiple tumor types including Bladder cancer and plays multiple roles in tumor cell proliferation and apoptosis. Previous study showed that miR-26a has different roles in different tumors and the expression of EZH2 is identified as a potential target of miR-26a which miR-26a has been found to decrease in bladder cancer. But the mechanism between EZH2 and miR-26a is not completely clear in bladder cancer. Western blot and Real-time PCR were involved to detect both expression of mRNA and protein of EZH2. And we used mimics-miR26a to elaborate the relationship between EZH2 and miR-26a in cell proliferation and apoptosis process through lots of specific assays. The results showed that EZH2 express mainly in bladder tumor tissues than para-carcinoma tissues. Meanwhile, miR26a can down-regulate the expression of EZH2 through suppressing EZH2 activity. Both miR26a and downregulated EZH2 can induce bladder cancer cell apoptosis and increase cell at G1 stage as well as suppress cell proliferation. The further assays reveal that miR-26a can suppress cell proliferation and enhance cell apoptosis through EZH2. In this study, we found that EZH2 was overexpressed in bladder tumor tissue and miR-26a could downregulate the expression of EZH2 to inhibit proliferation and enhance apoptosis in bladder cancer.