Curcumin Suppresses Colon Cancer In Vitro and In Vivo

Objective: To discuss In Vitro and In Vivo the effects of curcumin on colon cancer. Material and Methods: SW620 cell and nude mice with tumor were respectively divided into 3 groups: NC, low, middle, high and 5-Fu groups. Measuring the cell activity by MTT, the cell cycle and cell apoptosis using flow cytometry and relative proteins by WB assay in cell experiment. Evaluating tumor volume and weight, cell apoptosis rate by TUNEL assay and relative proteins by Immunohistochemistry (IHC). Results: Compared with NC group, the SW620 cell activity was significantly depressed with cell apoptosis and G1 phase rates increasing and PI3K, AKT and P53 proteins expression were significantly differences in curcumin treated groups with dose-dependent by WB assay; In Vivo study, the tumor volume and size were significantly suppressed and positive cell number were significantly up-regulation in curcumin treated groups with dose-dependent, and PI3K, AKT and P53 proteins expression were significantly differences in curcumin treated groups with dose-dependent by IHC. Conclusions: Curcumin had anti-tumor effects to colon cancer via regulation PI3K/AKT/P53 pathway In Vivo and vitro study.

A Study on the Skin Whitening Activity of Digesta from Edible Bird’s Nest: A Mucin Glycoprotein

Edible bird’s nest (EBN) is an unusual mucin glycoprotein. In China, it is popular among consumers due to its skin whitening activity. However, the relationship between protein, sialic acid, and the whitening activity of EBN after digestion is still unclear. In the present work, the whitening activity (antioxidant activity and tyrosinase inhibitory activity) of digested EBN were studied by HepG2 and B16 cell models. The dissolution rate of protein and sialic acid was 49.59% and 46.45% after the simulated digestion, respectively. The contents of free sialic acid and glycan sialic acid in EBN digesta were 17.82% and 12.24%, respectively. HepG2 cell experiment showed that the digested EBN had significant antioxidant activity, with EC50 of 1.84 mg/mL, and had a protective effect on H2O2-induced oxidative damage cells. The results of H2O2-induced oxidative damage showed that the cell survival rate increased from 40% to 57.37% when the concentration of digested EBN was 1 mg/mL. The results of the B16 cell experiment showed that the digested EBN had a significant inhibitory effect on tyrosinase activity, and the EC50 value of tyrosinase activity was 7.22 mg/mL. Cell experiments showed that free sialic acid had stronger antioxidant activity and tyrosinase inhibitory activity than glycan sialic acid. The contribution rate analysis showed that protein component was the main antioxidant component in digestive products, and the contribution rate was 85.87%; free sialic acid was the main component that inhibited tyrosinase activity, accounting for 63.43%. The products of the complete digestion of EBN are suitable for the development of a new generation of whitening health products.

Liposomal Artificial Red Blood Cell-Based Carbon Monoxide Donor Is a Potent Renoprotectant against Cisplatin-Induced Acute Kidney Injury

Cisplatin (CDDP) is an essential anti-tumor agent for chemotherapeutic regimens against various types of cancer. However, the progression of nephrotoxicity, which is the main adverse effect of CDDP, leads to discontinuation of CDDP chemotherapy. Therefore, development of a renoprotectant against CDDP-induced nephrotoxicity is crucial. Here, the potential of a carbon monoxide (CO)-loaded hemoglobin-vesicle (CO-HbV) as a renoprotectant for CDDP-induced nephrotoxicity was evaluated for its renoprotective effects against CDDP-induced nephrotoxicity, inhibitory effects on the anti-tumor activity of CDDP, and anti-tumor activity. In healthy mice, after pretreatment with either saline, HbV, or CO-HbV prior to CDDP administration, only the CO-HbV pretreatment group ameliorated the progression of CDDP-induced nephrotoxicity by suppressing apoptosis via caspase-3. In experiments using B16-F10 melanoma cells, the half-maximal inhibitory concentration of CDDP decreased with co-incubation with CO-HbV, owing to the anti-tumor activity of CO. CO-HbV pretreatment had no impact on the anti-tumor activity of CDDP in B16-F10 melanoma cell-bearing mice, which was consistent with the results of the cell experiment. Furthermore, CO-HbV pretreatment improved body growth and survival rates. In conclusion, CO-HbV pretreatment is a potent renoprotectant for CDDP-induced nephrotoxicity, allowing treatment with CDDP to be conducted without failure of cancer treatment.

Determining the architecture of nuclear ring of Xenopus laevis nuclear pore complex using integrated approaches

The nuclear pore complexes (NPCs) are large protein assemblies as a physical gate to regulate nucleocytoplasmic transport. Here, using integrated approaches including cryo-electron microscopy, hybrid homology modeling and cell experiment, we determined the architecture of the nuclear ring (NR) from Xenopus laevis oocytes NPC at subnanometer resolution. In addition to the improvement of the Y complex model, eight copies of Nup205 and ELYS were assigned in NR. Nup205 connects the inner and outer Y complexes and contributes to the assembly and stability of the NR. By interacting with both the inner Nup160 and the nuclear envelope (NE), the N-terminal β-propeller and α-solenoid domains of ELYS were found to be essential for accurate assembly of the NPC on the NE.

NAD+ Improved Experimental Autoimmune Encephalomyelitis by Regulating SIRT1 to Inhibit PI3K/ Akt /mTOR Signaling Pathway

Objective: To investigate the effect of NAD+ on thymus autophagy in experimental autoimmune encephalomyelitis (EAE) mice through SIRT1. Methods: Data sets GSE135511 and GSE131279 related to fatty liver in multiple sclerosis were downloaded from GEO database to search for differentially expressed genes. KEGG and GO pathway enrichment analysis was performed to construct PPI network, identify important modules and hub genes, and analyze the expression of hub genes. Animal experiments: Forty female C57BL/6 mice were randomly divided into 4 groups: control group, EAE group, NAD+ group and SIRT1 inhibitor group. The EAE model was prepared by MOG35-55 polypeptide immunoassay. The NAD+ group and SIRT1 inhibitor group were treated with NAD+ drug and fed for 4 weeks. The neurological function scores of the mice in each group were evaluated weekly. Cell experiment: The thymus tissues of wild-type mice were removed, ground and filtered into single-cell suspension, and then cultured. The thymus tissues were divided into four groups: control group, EAE group, NAD+ group and SIRT1 inhibitor group. MOG 35-55 (1μg/ mL) was given to induce EAE model in vitro. Both the NAD+ group and the SIRT1 inhibitor group were treated with NAD+. The expression of LC-3B was observed by immunofluorescence. The expressions of p-PI3K, p-AKT, p-mTOR, P62, Beclin1, LC-3B and SIRT1 were detected by WB. Results: Data sets GSE135511 and GSE131279 contained 95 up-regulated DEGs and 89 down-regulated DEGs. Enrichment analysis showed that it was mainly concentrated in PI3K-Akt-mTOR and autophagy pathway. SIRT1 was low expressed in the disease group. The EAE group, the NAD+ group and the SIRT1 inhibitor group all showed different degrees of morbidity. At week 2, there was no significant difference between the EAE group and the NAD+ group and the SIRT1 inhibitor group, but the neurological function score of the SIRT1 inhibitor group was significantly higher than that of the NAD+ group. The neurological function score of SIRT1 inhibitor group was the highest at 3 and 4 weeks. WB test showed that the expressions of P62, Beclin1, LC-3B and SIRT1 were the highest in the NAD+ group, while the expressions of p-PI3K, p-Akt and p-mTOR were the highest in the EAE group, followed by the SIRT1 inhibitor group, the NAD+ group and the control group. Cell experiment: Immunofluorescence showed that the fluorescence intensity of LC-3B in NAD+ group was the highest, followed by SIRT1 inhibitor group, EAE group, and control group. WB test showed that the expressions of P62, Beclin1, LC-3B and SIRT1 were the highest in the NAD+ group, followed by SIRT1 inhibitor group, EAE group and control group. The expressions of p-PI3K, p-AKT and p-mTOR were the highest in EAE group, followed by SIRT1 inhibitor group, NAD+ group and control group. Conclusion: NAD+ exerted a protective effect on EAE mice by inhibiting PI3K/ Akt /mTOR signaling pathway through SIRT1, and prevented EAE mice from sustained damage.

Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma

m6A RNA methylation regulators can regulate the growth, progression, and invasion of glioma cells by regulating their target genes, which provides a reliable support for the m6A regulator–target axes as the novel therapeutic targets and clinical prognostic signature in glioma. This study aimed to explore the role and prognostic value of m6A RNA methylation regulators and their targets. Expression profiles and clinicopathological data were obtained from the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteome Tumor Analysis Consortium (CPTAC) datasets. Differential expression and correlation analyses were performed between normal and glioma tissues at mRNA and protein levels. Univariate Cox regression, survival, and Lasso Cox regression analyses were conducted to identify and establish the prognostic gene signature. Kaplan–Meier curve, multivariate Cox regression analysis, and ROC were utilized to evaluate the prognostic capacity of the prognostic gene signature. The correlation analysis, systematic bioinformatics analysis, and cell experiment were performed to further understand the potential underlying molecular mechanisms and drug sensitivity. Our results suggested that IGF2BP2, KIAA1429, METTL16, and METTL3, as well as 208 targets are involved in the occurrence of glioma, GBM, and LGG. YTHDF1 and 78 targets involved the occurrence of glioma and GBM, not LGG, among which 181 genes were associated with overall survival. From other findings and our cell experiment results, we demonstrated that METTL3 can activate Notch pathway and facilitate glioma occurrence through regulating its direct targets NOTCH3, DLL3, and HES1, and Notch pathway genes may serve as the potential treatment targets for glioma. Our study established and validated a seven-gene signature comprising METTL3, COL18A1, NASP, PHLPP2, TIMP1, U2AF2, and VEGFA, with a good capability for predicting glioma survival, which may guide therapeutic customization and clinical decision-making. These genes were identified to influence 81 anticancer drug responses, which further contributes to the early phase clinical trials of drug development.

MOSCATO: A Supervised Approach for Analyzing Multi-Omic Single-Cell Data

Advancements in genomic sequencing continually improve personalized medicine in complex diseases. Recent breakthroughs generate multiple types of signatures (or multi-omics) from each cell, producing different data 'omic' types per single-cell experiment. We introduce MOSCATO, a technique for selecting features across multi-omic single-cell datasets that relate to clinical outcomes. For example, we leverage penalization concepts often used in multi-omic network analytics to accommodate the high-dimensionality where multiple-testing is likely underpowered. We organize the data into multi-dimensional tensors where the dimensions correspond to the different 'omic' types. Using the outcome and the single-cell tensors, we perform regularized tensor regression to return a variable set for each 'omic' type that forms the clinically-associated network. Robustness is assessed over simulations based on available single-cell simulation methods. Real data comparing healthy subjects versus subjects with leukemia is also considered in order to identify genes associated with the disease. The flexibility of our approach enables future extensions on distributional assumptions and covariate adjustments. This algorithm may identify clinically-relevant genetic patterns on a cellular-level that span multiple layers of sequencing data and ultimately inform highly precise therapeutic targets in complex diseases. Code to perform MOSCATO and replicate the real data application is publicly available on GitHub at https://github.com/lorinmil/MOSCATO and https://github.com/lorinmil/MOSCATOLeukemiaExample.

The Effects of Ginsenoside Rg2 on Trastuzumab-Induced Cardiotoxicity

Ginsenoside Rg2 inhibited the deterioration of cardiac function in rats, ginsenoside Rg2 inhibited cardiomyocyte apoptosis, increased the expression of Caspase-3,Caspase-9 and BAX in cell experiment. Conclusions: Ginsenoside Rg2 could protect cardiomyocytes in TZM-induced toxicity and it might be via inhibiting cell apoptosis.

3D printing of self-standing and vascular supportive multi-material hydrogel structures for organ engineering

Three dimensional printable formulation of self-standing and vascular-supportive structures using multi-materials suitable for organ engineering is of great importance and highly challengeable, but, it could advance the 3D printing scenario from printable shape to functional unit of human body. In this study, the authors report a 3D printable formulation of such self-standing and vascular-supportive structures using an in-house formulated multi-material combination of albumen/alginate/gelatin (A-SA-Gel)-based hydrogel. The rheological properties and relaxation behavior of hydrogels were analyzed prior to the printing process. The suitability of the hydrogel in 3D printing of various customizable and self-standing structures, including a human ear model, was examined by extrusion-based 3D printing. The structural, mechanical, and physicochemical properties of the printed scaffolds were studied systematically. Results supported the 3D printability of the formulated hydrogel with self-standing structures, which are customizable to a specific need. In vitro cell experiment showed that the formulated hydrogel has excellent biocompatibility and vascular supportive behavior with the extent of endothelial sprout formation when tested with human umbilical vein endothelial cells. In conclusion, the present study demonstrated the suitability of the extrusion-based 3D printing technique for manufacturing complex shapes and structures using multi-materials with high fidelity, which have great potential in organ engineering.