Hepatocellular carcinoma (HCC) is a common and deadly cancer with limited treatment options. Through genome‐wide growth depletion screens using clustered regularly interspaced short palindromic repeats and expression profiling of primary HCC tumors, we identified 13 clinically relevant target genes with therapeutic potential. Subsequent functional annotation analysis revealed significant enrichment of these 13 genes in the cell cycle, cell death, and survival pathways. Non–structural maintenance of chromosomes condensin I complex subunit G (NCAPG) was ranked the highest among the depletion screens and multiple HCC expression datasets. Transient inhibition of NCAPG using specific small interfering RNAs resulted in a significant reduction in cell growth, migration, and the down‐regulation of mitochondrial gene expression in vitro. Small homologous RNA–mediated knockdown of NCAPG significantly impaired cell viability, caused aberrant mitotic division, fragmented the mitochondrial network, and increased cell death in vitro. HCC cells with a reduced expression of NCAPG formed significantly smaller xenograft tumors in vivo. Importantly, high NCAPG expression was significantly associated with poorer overall and disease‐free survival in HCC patients. High NCAPG expression is a novel prognostic biomarker to predict HCC early recurrence after surgical resection. In conclusion, NCAPG is an essential gene for HCC tumor cell survival. It represents a promising novel target for treating HCC and a prognostic biomarker for clinical management of HCC.—Wang, Y., Gao, B., Tan, P. Y., Handoko, Y. A., Sekar, K., Deivasigamani, A., Seshachalam, V. P., OuYang, H.‐Y., Shi, M., Xie, C., Goh, B. K. P., Ooi, L. L., Hui, K. M. Genome‐wide CRISPR knockout screens identify NCAPG as an essential oncogene for hepatocellular carcinoma tumor growth. FASEB J. 33, 8759–8770 (2019). http://www.fasebj.org
Early tumor recurrence after curative surgical resection poses a great challenge to the clinical management of hepatocellular carcinoma (HCC). We conducted whole genome expression microarrays on 64 primary HCC tumors with clinically defined recurrence status and cross‐referenced with RNA‐seq data from 18 HCC tumors in the Cancer Genome Atlas project. We identified a 77‐gene signature, which is significantly associated with early recurrent (ER) HCC tumors. This ER‐associated signature shows significant enrichment in genes involved in cell cycle pathway. We performed receiver operating characteristic (ROC) analysis to evaluate the prognostic biomarker potential of these 77 genes and Pearson correlation analysis to identify 11 close clusters. The one gene with the best area under the ROC curve in each of the 11 clusters was selected for validation using reverse‐transcription quantitative PCR in an independent cohort of 24 HCC tumors. NUF2 was identified to be the minimal biomarker sufficient to discriminate ER tumors from LR tumors. NUF2 in combination with liver cirrhosis could significantly improve the detection of ER tumors with an AUROC of 0.82 and 0.85 in the test and validation cohort, respectively. In conclusion, NUF2 in combination with liver cirrhosis is a promising prognostic biomarker for early HCC recurrence.
The problem of an aging society is becoming increasingly acute. Diseases related to aging also come with it. There are some diseases that people can’t treat fundamentally. Therefore, people try to find a natural ingredient from natural medicine to treat these diseases and improve the quality of life of the elderly. With the screening of a large number of traditional Chinese medicines, we found that polysaccharides from Rehmannia glutinous (PRG) can prolong the lifespan of Caenorhabditis elegans (C. elegans). Neutral polysaccharide is the main component of PRG. In the present study, we used a C. elegans model to illustrate the stress resistance and lifespan extension effect and mechanism of two kinds of neutral polysaccharide fractions from Rehmannia glutinosa (NPRG), respectively called NPRRP and NPRR. Our data showed that two kinds of neutral polysaccharides fractions could extend the lifespan and delay senescence of wild-type worms. Moreover, the mechanism study revealed that NPRG was able to promote the nuclear localization of DAF-16 resulting in the activation of antioxidant enzymatic systems under oxidative stress. We also observed that NPRG didn’t increase the lifespan of mutants with daf-16 portion loss of function, suggesting NPRG prolonging the lifespan partially required the daf-16 gene on the insulin/IGF-1 signaling pathway (IIS). NPRG was found to have no effect on Escherichia coli OP50 (E. coli OP50) growth and pharyngeal pump movement of nematodes, indicating that the anti-aging effect of NPRG is not realized by the caloric restriction. However, mRNA levels of daf-2 were remarkably decreased after NPRG treatment. Thus daf-2 lost its inhibitory effect on the expression of daf-16 and had a continuous stimulation effect on the IIS, then prolonged the life of nematodes. Overall, our results illustrated the potential utilization of NPRG as a functional pharmaceutical ingredient to increase stress resistance and extend the life of C. elegans via the IIS, which could be developed as a natural supplement agent.
Radix aconite lateralis preparata (Fuzi), a folk medicine, has long been used for the treatment of diabetes and paralysis in China. We examined the effect of Fuzi alone on diabetic rats and Schwann cells in high glucose and the components responsible for its activity. The major constituents of FZE were identified by HPLC-MS/MS data. Male Sprague Dawley rats (n = 36) were randomly divided into control, diabetic, FZE 1.75 g/kg, FZE 3.50 g/kg, FZE 7.00 g/kg, and methylcobalamin groups. After two weeks treatment, nerve conduction velocity and paw withdrawal latency were measured. In vitro, the Schwann cells were grouped according to exposure: normal glucose (NG), normal glucose plus mannitol (NG+M), high glucose (HG), and HG plus different concentrations of FZE (0.1 µg/ml, 1.0 µg/ml, and 10.0 µg/ml). Oxygen free radicals and apoptosis were evaluated through DCFH2DA, DHE and annexin-PE/7-AAD assay, respectively. Apoptosis factors (Bax, Bcl-2, CytoC, caspase-3, and caspase-9) were analyzed using immunofluorescence. Nine alkaloids were identified. The results from animal model showed that FZE was effective in accelerating nerve conduction velocity and shortening paw withdrawal latency in diabetic rats. And in vitro, FZE was also found to protect Schwann cells against high glucose injury. FZE could significantly decrease the apoptotic ratio, superoxide anion and peroxide level. Furthermore, the apoptosis factors, including Bax, Bcl-2, CytoC, caspase-3, and caspase-9 were ameliorated in FZE treated groups. The HPLC-MSn method is simple and suitable for the identification of alkaloids in Fuzi. FZE has a protective effect in diabetic neuropathic rats, which is probably achieved by the antiapoptotic effect of FZE on Schwann cells. Apoptosis factor data imply that FZE protected Schwann cells through the mitochondria pathway. Alkaloids are major components contributing to the protective effect.
Quality consistency is one of the basic attributes of medicines, but it is also a difficult problem that natural medicines and their preparations must face. The complex chemical composition and comprehensive pharmacological action of natural medicines make it difficult to simply apply the commonly used evaluation methods in chemical drugs. It is thus urgent to explore the novel evaluation methods suitable for the characteristics of natural medicines. With the rapid development of analytical techniques and the deepening understanding of the quality of natural herbs, increasing numbers of researchers have proposed many new ideas and technologies. This review mainly focuses on the basic principles, technical characteristics and application examples of the chemical evaluation, biological evaluation methods and their combination in quality consistency evaluation of natural herbs. On the bases of chemical evaluation and clinical efficacy, new methods reflecting their pharmacodynamic mechanism and safety characteristics will be developed, and gradually towards accurate quality control, to achieve the goal of quality consistency. We hope that this manuscript can provide new ideas and technical references for the quality consistency of natural drugs and their preparations, thus better guarantee their clinical efficacy and safety, and better promote industrial development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.