Identification of domestic cat hepadnavirus from a cat blood sample in Japan

The hepatitis B virus (Hepadnaviridae) induces chronic hepatitis and hepatic cancer in humans. A novel domestic cat hepadnavirus (DCH) was recently identified in several countries, however, the DCH infection status of cats in Japan is unknown. Therefore, we investigated the DCH infection rate of 139 cat samples collected in Japan. We identified one positive blood sample (0.78%) from a 17-year-old female cat with chronically elevated alanine aminotransferase. Phylogenetic analysis demonstrated that the DCH strain identified in this study is genetically distinct from strains in other countries. Further investigations are required to elucidate the evolution of DCH and the impact of DCH infection on hepatic diseases in domestic cats.

4-Azidocinnoline—Cinnoline-4-amine Pair as a New Fluorogenic and Fluorochromic Environment-Sensitive Probe

A new type of fluorogenic and fluorochromic probe based on the reduction of weakly fluorescent 4-azido-6-(4-cyanophenyl)cinnoline to the corresponding fluorescent cinnoline-4-amine was developed. We found that the fluorescence of 6-(4-cyanophenyl)cinnoline-4-amine is strongly affected by the nature of the solvent. The fluorogenic effect for the amine was detected in polar solvents with the strongest fluorescence increase in water. The environment-sensitive fluorogenic properties of cinnoline-4-amine in water were explained as a combination of two types of fluorescence mechanisms: aggregation-induced emission (AIE) and excited state intermolecular proton transfer (ESPT). The suitability of an azide–amine pair as a fluorogenic probe was tested using a HepG2 hepatic cancer cell line with detection by fluorescent microscopy, flow cytometry, and HPLC analysis of cells lysates. The results obtained confirm the possibility of the transformation of the azide to amine in cells and the potential applicability of the discovered fluorogenic and fluorochromic probe for different analytical and biological applications in aqueous medium.

Uncovering the stability status of the reputed reference genes in breast and hepatic cancer cell lines

Accurate and reliable relative gene expression analysis via the Reverse Transcription-quantitative Real Time PCR (RT-qPCR) method strongly depends on employing several stable reference genes as normalizers. Utilization of the reference genes without analyzing their expression stability under each experimental condition causes RT-qPCR analysis error as well as false output. Similar to cancerous tissues, cancer cell lines also exhibit various gene expression profiles. It is crucial to recognize stable reference genes for well-known cancer cell lines to minimize RT-qPCR analysis error. In this study, we showed the expression level and investigated the expression stability of eight common reference genes that are ACTB, YWHAZ, HPRT1, RNA18S, TBP, GAPDH, UBC, and B2M, in two sets of cancerous cell lines. One set contains MCF7, SKBR3, and MDA-MB231 as breast cancer cell lines. Another set includes three hepatic cancer cell lines, including Huh7, HepG2, and PLC-PRF5. Three excel-based softwares comprising geNorm, BestKeeper, and NormFinder, and an online tool, namely RefFinder were used for stability analysis. Although all four algorithms did not show the same stability ranking of nominee genes, the overall results showed B2M and ACTB as the least stable reference genes for the studied breast cancer cell lines. While TBP had the lowest expression stability in the three hepatic cancer cell lines. Moreover, YWHAZ, UBC, and GAPDH showed the highest stability in breast cancer cell lines. Besides that, a panel of five nominees, including ACTB, HPRT1, UBC, YWHAZ, and B2M showed higher stability than others in hepatic cancer cell lines. We believe that our results would help researchers to find and to select the best combination of the reference genes for their own experiments involving the studied breast and hepatic cancer cell lines. To further analyze the reference genes stability for each experimental condition, we suggest researchers to consider the provided stability ranking emphasizing the unstable reference genes.

Association between Coffee Consumption/Physical Exercise and Gastric, Hepatic, Colon, Breast, Uterine Cervix, Lung, Thyroid, Prostate, and Bladder Cancer

Although the effects of coffee consumption and physical exercise on the risk of cancer have been suggested, their interactions have not been investigated. The present cross-sectional study aimed to investigate the correlation of coffee consumption and physical exercise with cancer. Participants ≥40 years old in the Korean Genome and Epidemiology Study 2004–2016 were included (n = 162,220). Histories of gastric cancer, hepatic cancer, colon cancer, breast cancer, uterine cervix cancer, lung cancer, thyroid cancer, prostate cancer, and bladder cancer were analyzed according to the coffee consumption groups using logistic regression models. The odds among individuals in the >60 cups/month coffee group were lower for gastric cancer (adjusted odds ratio (aOR) = 0.80 (95% confidence intervals = 0.65–0.98)), hepatic cancer (0.32 (0.18–0.58)), colon cancer (0.53 (0.39–0.72)), breast cancer (0.56 (0.45–0.70)), and thyroid cancer (0.71 (0.59–0.85)) than for individuals in the no coffee group. Physical exercise of ≥150 min/week was correlated with higher odds for gastric cancer (1.18 (1.03–1.36)), colon cancer (1.52 (1.26–1.83)), breast cancer (1.53 (1.35–1.74)), thyroid cancer (1.42 (1.27–1.59)), and prostate cancer (1.61 (1.13–2.28)) compared to no exercise. Coffee consumption and physical exercise showed an interaction in thyroid cancer (p = 0.002). Coffee consumption was related to a decreased risk of gastric cancer, hepatic cancer, colon cancer, breast cancer, and thyroid cancer in the adult population. Physical exercise was positively correlated with gastric cancer, colon cancer, breast cancer, thyroid cancer, and prostate cancer.

Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment

In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.