Cyclic production of biocompatible few-layer graphene ink with in-line shear-mixing for inkjet-printed electrodes and Li-ion energy storage

The scalable production of two-dimensional (2D) materials is needed to accelerate their adoption to industry. In this work, we present a low-cost in-line and enclosed process of exfoliation based on high-shear mixing to create aqueous dispersions of few-layer graphene, on a large scale with a Yw ~ 100% yield by weight and throughput of ϕ ~ 8.3 g h−1. The in-line process minimises basal plane defects compared to traditional beaker-based shear mixing which we attribute to a reduced Reynolds number, Re ~ 105. We demonstrate highly conductive graphene material with conductivities as high as σ ∼ 1.5 × 104 S m−1 leading to sheet-resistances as low as Rs ∼ 2.6 Ω □−1 (t ∼ 25 μm). The process is ideal for formulating non-toxic, biocompatible and highly concentrated (c ∼ 100 mg ml−1) inks. We utilise the graphene inks for inkjet printable conductive interconnects and lithium-ion battery anode composites that demonstrate a low-rate lithium storage capability of 370 mAh g−1, close to the theoretical capacity of graphite. Finally, we demonstrate the biocompatibility of the graphene inks with human colon cells and human umbilical vein endothelial cells at high c ∼ 1 mg ml−1 facilitating a route for the use of the graphene inks in applications that require biocompatibility at high c such as electronic textiles.

Increased ENT2 Expression and Its Association With Altered Purine Metabolism in Different Stages of Colorectal Cancer Cell Lines

Background Colorectal cancer (CRC) is one of the most prevalent malignant cancers worldwide. Although the purine metabolism pathway is known to be vital for cancer cells survival mechanism, not much is known on ENT2 role in CRC development and its association with purine metabolites. Hence this study is aimed to determine the level of hypoxanthine phosphoribosyl transferase (HPRT), hypoxanthine, uric acid (UA), and the activity of xanthine oxidase (XO) and relate the findings with the ENT2 expression level in different CRC stages. Methods and results Normal colon cell line; CCD-841CoN and a panel of human CRC cell lines; SW480, HCT15 and HCT116, representing different CRC stages; Dukes’ B, C, and D respectively, have been used to measure HPRT, hypoxanthine/xanthine, UA levels and the activity of XO by biochemical assays. The level of ENT2 gene expression was also performed by qRT-PCR. The levels of HPRT, hypoxanthine were significantly higher (P< 0.05), while XO and UA were lower (P< 0.05) in all CRC stages as compared to the normal colon cells. Furthermore, ENT2 expression was found to be increased in all CRC stages. Despite having the highest level of HPRT and hypoxanthine, ENT2 level is lower in Dukes' D when compared to Dukes' B and C. Conclusion The rate of salvage pathway is increased in CRC development as indicated by the elevated levels of HPRT and hypoxanthine in different CRC stages. Increase ENT2 expression implies its importance in assisting hypoxanthine uptake. This step is vital in order to increase DNA synthesis via hypoxanthine recycling. Thus, ENT2 may be a potential marker in therapeutic development.

Novel Herbal Formulation Jing Si Exhibits Multiple Functions to Inhibit Replication Activity and Subsides Viral Load of COVID-19 Variants

Background: SARS-CoV-2 is susceptible to frequent mutations and gets transformed into variants therefore identifying novel multi targeting remedies is necessary in formulating strategies to overcome the pandemic. Methods: Traditional Chinese medicine based formula Jing Si herbal (JSH) was screened and analyzed by HPLC to evaluate its ability to act against infection by SARS-CoV-2 variants. The 3CL protease and RdRp assay kit were utilized to detect the enzyme activity. In order to determine the effect of JSH on the binding efficiency and viral penetration of SARS-CoV-2 variants, Calu-3 lung cells and Caco-2 colon cells were infected with fluorescent SARS-CoV-2 pseudo type lentiviruses. In addition, the effect of JSH (16.22 mg /mice/day and 48.66 mg/mice/day) on the viral load in SKH1J mice exposed to inhalation of luminescent SARS-CoV-2 variants for three days was determined. Results: The JSH was found to be effective in inhibiting the viral entry into Calu-3 and Caco-2 cells and in mice pre-treated with JSH for 3 days also inhibited the viral load exposed to different SARS-CoV-2 variants. Interestingly, JSH also decreased 3cL and RdRp activity thereby revealing the multi targeting nature of JSH and therefore will be a potential preventive SARS-CoV-2 infection.Conclusion: Taken together, our present results revealed that JSH could be a potential candidate for COVID-19 treatment.

Degradation of Selected Antidepressants Sertraline and Citalopram in Ultrapure Water and Surface Water Using Gamma Radiation

Gamma radiation was applied to degradation selected antidepressants in ultrapure water and surface water. Additionally, the influence of typical radical scavengers like carbonate, nitrate and humic acid was determined. The cytotoxicity towards liver cells HepG2 and colon cells Caco2 were measured during the radiation process. It was found that radiation technology, specifically ionizing radiation, can achieve satisfactory degradation efficiency with both SER and CIT. It was shown that the process of decomposition of the tested antidepressants with the highest efficiency occurs in the reaction with the hydroxyl radical.

Effects of Sargassum plagiophyllum extract pretreatment on tissue histology of constipated mice

Purpose: To evaluate the toxicity of the dried seaweed, Sargassum plagiophyllum, extract (SPE) pretreatment in constipated mice.Methods: The dried seaweed powder was mixed with distilled water and extracted by autoclave at 121°C. Antioxidant activity of the extract was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Human normal colon cells were pretreated with SPE at 0 - 100 μg/mL for 24 h before challenging them with 100 μM hydrogen peroxide (H2O2). Intracellular reactive oxygen species (ROS) were quantified using 2',7'- dichlorodihydrofluorescein diacetate (H2DCFDA). Male ICR mice were pretreated for 14 consecutive days with SPE at 100, 500 and 1,000 mg/kg or lactulose at 500 mg/kg. Body weight and food intake were recorded daily. Constipation was induced with loperamide on days 12, 13 and 14 and fecal pellets evacuated over a 4-hr period. The ileum, liver, kidney, and spleen were collected for histopathological examination.Results: The IC50 for the radical scavenging capacity of SPE was 343.90 ± 4.21 μg/mL compared to 14.14 ± 0.71 μg/mL for ascorbic acid. Pretreatment with SPE was significantly reduced ROS production in human normal colon cells. Oral administration of all doses of SPE and lactulose for 14 consecutive days had no effect on food intake or body weight when compared to the normal control group. Defecation was significantly more frequent in mice pretreated with SPE at 100 mg/kg than in the constipation control group. Histopathological examination of the ileum, liver, kidney and spleen of pretreated constipated mice revealed no toxic effect from either SPE or lactulose. On the other hand, the loss of mucus-producing cells in the ileum of constipated mice was significantly lower in mice pretreated with SPE.Conclusions: These findings support the safety of SPE supplementation and may broaden itsapplication in clinical fields as an alternative drug or supplement for constipation management.

Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells

Overheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules is the incorporation of fluorine atoms in the chemical structure, since fluor can tune some chemical properties such as binding affinity. Herein we report the anticancer effect of gold derivatives with phosphanes derived from 1,3,5-triaza-7-phosphaadamantane (PTA) with long hydrocarbon chains and the homologous fluorinated chains. Besides, we analysed the influence of temperature in the cytotoxic effect. The studied gold(I) complexes with phosphanes derived from PTA showed antiproliferative effect on human colon carcinoma cells (Caco-2/TC7 cell line), probably by inhibiting cellular TrxR causing a dysfunction in the intracellular redox state. In addition, the cell cycle was altered by the activation of p53, and the complexes produce apoptosis through mitochondrial depolarization and the consequent activation of caspase-3. Furthermore, the results suggest that this cytotoxic effect is enhanced by hyperthermia and the presence of polyfluorinated chains.

Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism

In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management of CRC and urges need for new leads of anticancer drugs. We demonstrate that CRC treatment with the phytopharmaceutical mangiferin (MGF), a glucosylxanthone present in Mango tree stem bark and leaves (Mangifera Indica L.), induces dose-dependent tumor regression and decreases lung metastasis in a syngeneic immunocompetent allograft mouse model of murine CT26 colon carcinoma, which increases overall survival of mice. Antimetastatic and antiangiogenic MGF effects could be further validated in a wound healing in vitro model in human HT29 cells and in a matrigel plug implant mouse model. Interestingly, transcriptome pathway enrichment analysis demonstrates that MGF inhibits tumor growth, metastasis and angiogenesis by multi-targeting of mitochondrial oxidoreductase and fatty acid β-oxidation metabolism, PPAR, SIRT, NFκB, Stat3, HIF, Wnt and GP6 signaling pathways. MGF effects on fatty acid β-oxidation metabolism and carnitine palmitoyltransferase 1 (CPT1) protein expression could be further confirmed in vitro in human HT29 colon cells. In conclusion, antitumor, antiangiogenic and antimetastatic effects of MGF treatment hold promise to reduce adverse toxicity and to mitigate therapeutic outcome of colorectal cancer treatment by targeting mitochondrial energy metabolism in the tumor microenvironment.

Colon Cancer-Related Genes Identification and Function Study Based on Single-Cell Multi-Omics Integration

Transcriptomes and DNA methylation of colon cancer at the single-cell level are used to identify marker genes and improve diagnoses and therapies. Seven colon cancer subtypes are recognized based on the single-cell RNA sequence, and the differentially expressed genes regulated by dysregulated methylation are identified as marker genes for different types of colon cancer. Compared with normal colon cells, marker genes of different types show very obvious specificity, especially upregulated genes in tumors. Functional enrichment analysis for marker genes indicates a possible relation between colon cancer and nervous system disease, moreover, the weak immune system is verified in colon cancer. The heightened expression of markers and the reduction of methylation in colon cancer promote tumor development in an extensive mechanism so that there is no biological process that can be enriched in different types.

Anti-Cancer Properties of Coix Seed Oil against HT-29 Colon Cells through Regulation of the PI3K/AKT Signaling Pathway

This study aims to observe the effects of coix seed oil (CSO) on HT-29 cells and investigate its possible regulation mechanism of the PI3K/Akt signaling pathway. Fatty acid analysis showed that coix seed oil mainly contains oleic acid (50.54%), linoleic acid (33.76%), palmitic acid (11.74%), and stearic acid (2.45%). Fourier transform infrared results found that the fatty acid functional groups present in the oil matched well with the vegetable oil band. The results from CCK-8 assays showed that CSO dose-dependently and time-dependently inhibited the viability of HT-29 cells in vitro. CSO inhibited cell viability, with IC50 values of 5.30 mg/mL for HT-29 obtained after 24 h treatment. Morphological changes were observed by apoptotic body/cell nucleus DNA (Hoechst 33258) staining using inverted and fluorescence microscopy. Moreover, flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. It showed that CSO induced cell apoptosis and cycle arrest in the G2 phase. Quantitative real-time PCR and Western blotting revealed that CSO induced cell apoptosis by downregulating the PI3K/AKT signaling pathway. Additionally, CSO can cause apoptosis in cancer cells by activating caspase-3, up-regulating Bax, and down-regulating Bcl-2. In conclusion, the results revealed that CSO induced G2 arrest and apoptosis of HT-29 cells by regulating the PI3K/AKT signaling pathway.

Nigella Sativa’s Protection Against 7,12 Dimethylbenz [A] Anthracene -Induced Colon Carcinogenesis in Rats

Colon cancer is the third most common cause of death from cancer worldwide. Recently, natural products have been widely used as an alternative therapy for colon cancer. Previous studies have reported that Nigella sativa has chemopreventive activity in vitro and in vivo.This study aimed to evaluate the effect of Nigella sativa seed (NSS) on rat-colon cell after initiation of 7,12-dimethylbenz [a] anthracene. Rats were divided into five groups, 12 rats in each group: Group I was given 7,12dimetilbenz [a] anthracene (DMBA) orally 20 mg/kgBW twice a week for five weeks, group V is the solvent control group was given corn oil. The other three groups were given DMBA + NSS, at the dosage of 250 mg/kgBW, 500 mg/kgBW and 750 mg/kgBW. NSS extract was dissolved in corn oil and administered daily per oral during the next two weeks before and during the initiation of DMBA. After 16 weeks, all rats were sacrificed. H&E staining showed that necrosis activity was lower in treated groups compared to DMBA group. AgNOR staining showed mAgNOR was significantly decrease following the increasing dose of NSS (250 mg/kgBW, 500 mg/kgBW and 750 mg/kgBW) were subsequently 1.62 ± 0.086, 1.60 ± 0.101 and 1.39 ± 0.049 (p<0.05). The results showed that NNS reduce the damage of colon cells and inhibit colon cell proliferation in DMBA induced rats.