ATIP/ATIP1 regulates prostate cancer metastasis through mitochondrial dynamic-dependent signaling.

Mitochondria play a fundamental role in cell survival and motility. Abnormalities in mitochondria are associated with carcinogenesis, especially with tumor metastasis. In this study, we explore the biological function of ATIP1, which is a mitochondrial-located isoform of angiotensin II AT2 receptor interacting proteins (ATIPs) in prostate cancer cells. The results showed that ATIP is downregulated in prostate cancer tissues and is negatively correlated with the disease-free survival rate of prostate cancer patients. Silencing of ATIP promotes mitochondrial fission and enhances tumor cell migration and invasion. Reconstitution of ATIP1 in ATIP-deficient cells significantly attenuates mitochondrial trafficking and tumor cell movement. Therefore, ATIP1 is a negative regulator of mitochondrial dynamics and tumor cell motility and is also a potential biomarker for predicting prostate cancer malignancy.

Investigation of CuCoFe-LDH as an efficient and stable catalyst for the degradation of acetaminophen in heterogeneous electro-Fenton system: Key operating parameters, mechanisms and pathways.

Pharmaceuticals, as anthropogenic pollutants in a wide range of water sources, generally require specific treatment methods for degradation. A trimetallic layered double hydroxide (CuCoFe-LDH) was successfully fabricated by coprecipitation and applied as a novel heterogeneous electro-Fenton (EF) catalyst for the degradation of acetaminophen (ACT) from aqueous environments. The EF experiments showed that the CuCoFe-LDH/EF process achieved 100% of ACT degradation efficiency within 60 min at pH = 5, catalyst dosage of 0.50 g/L, current density of 10 mA/cm2 and initial ACT concentration of 20 mg/L. An impressive (>80%) mineralization of ACT was obtained over a wide pH range (pH 3-9) after 180 min. Meanwhile, the role of ·OH and O2.- were certified by radical quenching experiments and electron paramagnetic resonance (EPR) analysis. Through mechanism exploration, the coexistence of Cu and Co on Fe-based LDHs can accelerate the interfacial electron transfer and promote the formation of the reactive oxygen species (ROS), thus facilitating the EF process. Furthermore, the degradation by-products and possible degradation pathways of ACT in the CuCoFe-LDH/EF process were proposed. The reusability test and the treatment of various typical organic pollutants experiments indicated that the CuCoFe-LDH/EF process has excellent stability and broad application prospects. This work provides a valuable reference for the treatment of pharmaceuticals by the heterogeneous EF process in a wide range of pH.

The mechanism of carbon source utilization by microalgae when co-cultivated with photosynthetic bacteria.

Microalgae-photosynthetic bacteria (PSB) co-culture, which is promising for wastewater treatment and lipid production, is lacking of study. In this work, the combinations of 3 microalgae and 3 PSB strains were firstly screened and then different inoculation ratios of the co-cultures were investigated. It was found the best promotion was Chlorella pyrenoidosa/Rhodobacter capsulatus co-culture (1:1), where the biomass productivity, acetate assimilation rate and lipid productivity were 1.64, 1.61 and 2.79 times than that of the sum of pure microalgae and PSB cultures, respectively. Meanwhile, the inoculation ratio significantly affected the growth rate and lipid productivity of co-culture systems. iTRAQ analysis showed that PSB played a positive effect on acetate assimilation, TCA cycle and glyoxylate cycle of microalgae, but decreased the carbon dioxide utilization and photosynthesis, indicating PSB promoted the microalgae metabolism of organic carbon utilization and weakened inorganic carbon utilization. These findings provide in-depth understanding of carbon utilization in microalgae-PSB co-culture.

Cytotoxic withanolide constituents of Physalis longifolia.

Fourteen new withanolides, 1-14, named withalongolides A-N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15-22). The structures of compounds 1-14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS viability assay, eight withanolides (1, 2, 3, 7, 8, 15, 16, and 19) and four acetylated derivatives (1a, 1b, 2a, and 2b) showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells with IC50 values in the range between 0.067 and 9.3 µM.

The Impact of the Closure of the Live Poultry Market due to COVID-19 on the Avian Influenza Virus in Nanchang, Jiangxi Province, China.

This article aims to understand the changes in the detection rates of H5, H7, and H9 subtypes of avian influenza viruses (AIVs) in the live poultry markets (LPMs) in Nanchang City, Jiangxi Province, before and after the outbreak of the COVID-19. From 2019 to 2020, we monitored the LPM and collected specimens, using real-time reverse transcription polymerase chain reaction technology to detect the nucleic acid of type A AIV in the samples. The H5, H7, and H9 subtypes of influenza viruses were further classified for positive results. We analyzed 1,959 samples before and after the outbreak and found that the positive rates of avian influenza A virus (39.69%) and H9 subtype (30.66%) after the outbreak were significantly higher than before the outbreak (26.84% and 20.90%, respectively; P < 0.001). In various LPMs, the positive rate of H9 subtypes has increased significantly (P ≤ 0.001). Positive rates of the H9 subtype in duck, fecal, daub, and sewage samples, but not chicken samples, have increased to varying degrees. This study shows that additional measures are needed to strengthen the control of AIVs now that LPMs have reopened after the relaxing of COVID-19-related restrictions.

Withaferin A, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma.

As part of a program to discover drug leads from plant biodiversity, the present investigation was undertaken to explore the anticancer potential of compounds derived from selected Latin American plants. Bioassay-guided fractionation of a crude extract of the aerial parts of Vassobia breviflora led to the isolation of the withanolide-type steroidal lactone withaferin A (1). This compound was tested for antiproliferative activity against the head and neck squamous cell carcinoma (HNSCC) cell lines, MDA1986, JMAR, UM-SCC-2, and JHU011. The inhibitory concentrations to reduce cell viability to 50% (IC(50)) were determined by the MTS cytotoxicity assay, and 1 reduced cell viability with IC(50) values in the range 0.5-2.2 µM. A mechanistic study showed that 1 induces apoptosis and cell death in HNSCC cells as well as a cell-cycle shift from G(0)/G(1) to G(2)/M. Cells treated with 1 exhibited inactivation of Akt and a reduction in total Akt concentration. This investigation constitutes the first report of the antiproliferative activity of withaferin A (1) against head and neck squamous carcinoma.

Alternatively activated NUSAP1 promotes tumor growth and indicates poor prognosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality. The key genes involved in initiation and development of HCC is not entirely clear. METHODS: We performed a meta-analysis of available transcriptome data from 6 independent HCC datasets [5 datasets from the Gene Expression Omnibus (GEO) and 1 dataset from The Cancer Genome Atlas (TCGA)]. The associations of the nucleolar and spindle-associated protein 1 (NUSAP1) expression level with clinicopathological factors and survival times were analyzed. Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when NUSAP1 expression was inhibited by shNUSAP1. RESULTS: Based on the transcriptome and survival data in the GEO and TCGA databases, NUSAP1 gene was markedly upregulated in HCC. High expression of NUSAP1 in HCC is related to the iCluster1 molecular subgroup, poor survival, poor tumor differentiation and TNM stage. Additionally, pathway analysis based on RNAseq data suggested that NUSAP1 could activate the expression of genes involves in cell proliferation. Furthermore, downregulation of NUSAP1 expression could significantly inhibit the proliferation of SMMC-7721 and Huh7 cells in vitro. CONCLUSIONS: Our study provides evidence that NUSAP1 may serve as a candidate prognostic marker and a target for future therapeutic intervention in HCC.

Identification of core genes in ovarian cancer by an integrative meta-analysis.

BACKGROUND: Epithelial ovarian cancer is one of the most severe public health threats in women. Since it is still challenging to screen in early stages, identification of core genes that play an essential role in epithelial ovarian cancer initiation and progression is of vital importance. RESULTS: Seven gene expression datasets (GSE6008, GSE18520, GSE26712, GSE27651, GSE29450, GSE36668, and GSE52037) containing 396 ovarian cancer samples and 54 healthy control samples were analyzed to identify the significant differentially expressed genes (DEGs). We identified 563 DEGs, including 245 upregulated and 318 downregulated genes. Enrichment analysis based on the gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the upregulated genes were significantly enriched in cell division, cell cycle, tight junction, and oocyte meiosis, while the downregulated genes were associated with response to endogenous stimuli, complement and coagulation cascades, the cGMP-PKG signaling pathway, and serotonergic synapse. Two significant modules were identified from a protein-protein interaction network by using the Molecular Complex Detection (MCODE) software. Moreover, 12 hub genes with degree centrality more than 29 were selected from the protein-protein interaction network, and module analysis illustrated that these 12 hub genes belong to module 1. Furthermore, Kaplan-Meier analysis for overall survival indicated that 9 of these hub genes was correlated with poor prognosis of epithelial ovarian cancer patients. CONCLUSION: The present study systematically validates the results of previous studies and fills the gap regarding a large-scale meta-analysis in the field of epithelial ovarian cancer. Furthermore, hub genes that could be used as a novel biomarkers to facilitate early diagnosis and therapeutic approaches are evaluated, providing compelling evidence for future genomic-based individualized treatment of epithelial ovarian cancer.

Chlorinated Withanolides from Withania somnifera.

A chlorinated withanolide, 6α-chloro-5ß,17α-dihydroxywithaferin A (1), and nine known withanolides, 6α-chloro-5ß-hydroxywithaferin A (2), (22R)-5ß-formyl-6ß,27-dihydroxy-1-oxo-4-norwith-24-enolide, withaferin A, 2,3-dihydrowithaferin A, 3-methoxy-2,3-dihydrowithaferin A, 2,3-didehydrosomnifericin, withanone, withanoside IV and withanoside X, were isolated from Withania somnifera (Solanaceae). All structures were elucidated on the basis of spectroscopic methods (IR, HRESIMS, 1D/2D NMR). X-ray crystallography confirmed the absolute configuration of 1.