Molecular docking analysis of fluoroquinolones and other natural and synthetic compounds with the HCV NS3 helicase.

It is of an interest to document the molecular docking analysis of fluoroquinolones and other natural and synthetic compounds with the HCV NS3 helicase. Data shows that three fluoroquinolones interacted with the NS3 helicase in the catalytic region, targeting some of the amino acids known to play a crucial role in NS3 helicase activity. Similarly, binding energy shows that the fluoroquinolones were comparable to the thiazolpiperazinyl derivatives, while superior to several of the synthetic and natural derivatives. The results show three fluoroquinolones to be potent helicase inhibitors that can be repurposed as supplemental therapy against HCV especially in cases non-responsive to DAAAs.

Machine learning-based diagnosis of melanoma using macro images.

Cancer bears a poisoning threat to human society. Melanoma, the skin cancer, originates from skin layers and penetrates deep into subcutaneous layers. There exists an extensive research in melanoma diagnosis using dermatoscopic images captured through a dermatoscope. While designing a diagnostic model for general handheld imaging systems is an emerging trend, this article proposes a computer-aided decision support system for macro images captured by a general-purpose camera. General imaging conditions are adversely affected by nonuniform illumination, which further affects the extraction of relevant information. To mitigate it, we process an image to define a smooth illumination surface using the multistage illumination compensation approach, and the infected region is extracted using the proposed multimode segmentation method. The lesion information is numerated as a feature set comprising geometry, photometry, border series, and texture measures. The redundancy in feature set is reduced using information theory methods, and a classification boundary is modeled to distinguish benign and malignant samples using support vector machine, random forest, neural network, and fast discriminative mixed-membership-based naive Bayesian classifiers. Moreover, the experimental outcome is supported by hypothesis testing and boxplot representation for classification losses. The simulation results prove the significance of the proposed model that shows an improved performance as compared with competing arts.

DNA methyltransferase 1, 3a, and 3b expression in hepatitis C associated human hepatocellular carcinoma and their clinicopathological association.

Identification of biomarker will obligate a substantial influence on various cancer management and treatment. We hypothesize that genetic/proteomic and epigenetic studies should be uncovering modifications which may be independently or jointly affect the expression of the genes that are involved in the progression of liver cancer (LC). For this purpose, we examined the effect of expressional changes of DNMTs on HCV infected LC of different genotypes. We found that both mRNA and protein expression levels of DNMT1, 3a, and 3b were upregulated in genotype 1b and 3a HCV infected patients as compared to control. However, DNMT3b mRNA levels did not change in genotypes 2a, 3, and 4, but were upregulated at the protein level by genotype 1b, 2a, and 3a. Furthermore, no significant changes were observed for DNMTs investigated in sample expressing the genotypes 5 and 6. Our findings suggest that HCV at least in part by altering DNMTs expression may play a significant role in HCC progression.

Introducing differential expression of human heat shock protein 27 in hepatocellular carcinoma: moving toward identification of cancer biomarker.

Previously, it has to be acknowledged that overexpressed heat shock protein B27 (HSPB27) have been implicated in the etiology of wide range of human cancers. However, the molecular mechanism leading to the disease initiation to progression in liver cancer is still unknown. Present work was undertaken to investigate the differentially expressed HSPB27 in association with those damages that lead to liver cancer development. For the identification of liver cancer biomarker, samples were subjected to comparative proteomic analysis using two-dimensional gel electrophoresis (2-DE) and were further validated by Western blot and immunohistochemical analysis. After validation, in silico studies were applied to demonstrate the significantly induced phosphorylated and S-nitrosylated signals. The later included the interacting partner of HSPB27, i.e., mitogen-activated protein kinase-3 and 5 (MAPK3 and 5), ubiquitin C (UBC), v-akt murine thymoma viral oncogene homolog 1 (AKT1), mitogen-activated protein kinase 14 (MAPK14), and tumor protein p53 (TP53), which bestowed with critical capabilities, namely, apoptosis, cell cycling, stress activation, tumor suppression, cell survival, angiogenesis, proliferation, and stress resistance. Taking together, these results shed new light on the potential biomarker HSPB27 that overexpression of HSPB27 did lead to upregulation of their interacting partner that together demonstrate their possible role as a novel tumor progressive agent for the treatment of metastasis in liver cancer. HSPB27 is a promising diagnostic marker for liver cancer although further large-scale studies are required. Also, molecular profiling may help pave the road to the discovery of new therapies.