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Background: MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed. Methods: MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT–PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. Results: Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay. Conclusion: MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.

The vascular endothelial growth factor receptor 2 (VEGFR-2) is considered one of the most studied therapeutic targets for the treatment of various cancers. Among many heterocyclic compounds, the oxadiazole derivatives have been reported to exhibit significant anticancer activities. Therefore, exploring these derivatives against VEGFR-2 could provide valuable drug molecules that can be safely utilized for cancer treatment. In this study, a wide range of computational techniques, including quantitative structure-activity relationship (QSAR) modeling, molecular docking, and molecular dynamics simulation studies, were used for the systematic development and investigation of oxadiazole derivatives. Twenty-one new oxadiazole derivatives were synthesized based on a QSAR modeling technique applied to 50 reported oxadiazole compounds with a wide range of anticancer activities. Seven parent compounds, that is, S39 to S45, along with their newly prepared derivatives, were subjected to the developed QSAR model for the prediction of their IC[sub.50] values. All the new derivatives were then redocked using AutoDock Vina software to validate the QSAR results. Of the 21 new derivatives, S43b, S44b, and S45b exhibited significantly improved activity compared to the parent compounds. The results were further validated through molecular dynamics simulation studies. All the results of this study provide a guiding pathway for the design and development of new oxadiazole moieties with better anticancer activity.

Dedifferentiation and inflammation are major features of cartilage degeneration during the pathogenesis of osteoarthritis (OA). Thymoquinone (TQ) is the major compound of black seed oil isolated from Nigella sativa with various beneficial or harmful effects on several diseases; however, its effects on the dedifferentiation and inflammation of chondrocytes have not yet been characterized. In the present study, we investigated whether TQ regulates the dedifferentiation and inflammation of rabbit articular chondrocytes, focusing on the production of reactive oxygen species (ROS) in rabbit articular chondrocytes. TQ induced the generation of ROS in a dose-dependent manner, as shown by staining with the fluorescent probe, 2′-7′-dichlorofluorescein diacetate. We confirmed that TQ induced dedifferentiation by measuring the loss of type II collagen and the reduction in chondroitin sulfate proteoglycan levels. TQ also caused inflammation by inducing the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). The antioxidant, N-acetyl cysteine (NAC), prevented the dedifferentiation and inflammation which was generated by the TQ-induced production of ROS. Furthermore, TQ caused a dose-dependent increase in p38, phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphoinositide 3-kinase (PI3K) expression. NAC abrogated this effect and attenuated the dedifferentiation and inflammation which was generated by the TQ-induced production of ROS. To identify the ROS-regulated pathways, we treated the chondrocytes with the p38 inhibitor, SB203580, the MEK inhibitor, PD98059, and the PI3K inhibitor, LY294002. PD98059 inhibited the TQ-induced dedifferentiation and SB203580 and LY294002 prevented the TQ-induced inflammation. These findings suggest that the TQ-induced production of ROS causes dedifferentiation through the ERK pathway and inflammation through the PI3K and p38 pathways in rabbit articular chondrocytes.

Formal concept analysis (FCA) is largely applied in different areas. However, in some FCA applications the volume of information that needs to be processed can become unfeasible. Thus, the demand for new approaches and algorithms that enable processing large amounts of information is increasing substantially. This article presents a new algorithm for extracting proper implications from high-dimensional contexts. The proposed algorithm, called ImplicPBDD, was based on the PropIm algorithm, and uses a data structure called binary decision diagram (BDD) to simplify the representation of the formal context and enhance the extraction of proper implications. In order to analyze the performance of the ImplicPBDD algorithm, we performed tests using synthetic contexts varying the number of objects, attributes and context density. The experiments show that ImplicPBDD has a better performance—up to 80% faster—than its original algorithm, regardless of the number of attributes, objects and densities.

This study aimed to evaluate the oncological and voice outcomes of transoral laser microsurgery for tumour stage T1b stage glottic cancer patients. A prospective cohort study in a tertiary care head and neck cancer centre included tumour-node-metastasis stage T1bN0M0 glottic cancer patients scheduled to undergo transoral laser microsurgery from January 2002 until June 2014. Kaplan-Meier five-year analyses of local control, overall survival, disease-specific survival and laryngeal preservation were performed. Voice Handicap Index-10 scores and maximum phonation times were also recorded. Twenty-one participants with a mean age of 66.8 years were enrolled. The mean follow up was 56.5 months. Kaplan-Meier 5-year survival analysis illustrated a local control rate of 82 per cent, overall survival of 88 per cent, disease-specific survival of 100 per cent, and laryngeal preservation of 100 per cent. The pre-operative Voice Handicap Index-10 score was 19.1 ± 9.47 (mean ± standard deviation (SD)) and the post-operative scores were 13.5 ± 9.29 at three months, 10.44 ± 9.70 at one year and 5.83 ± 4.91 at two years. The pre-operative maximum phonation time was 16.23 ± 5.46 seconds (mean ± SD) and the post-operative values were 14.44 ± 6.73 seconds at three months, 15.27 ± 5.71 seconds at one year and 14.33 ± 6.44 seconds at two years. Transoral laser microsurgery yields relatively high rates of oncological control and acceptable voice outcomes, and thus shows utility as a primary treatment modality for T1b glottic cancer.

In this paper, we present a set of algorithms to display a Hasse diagram of triadic concepts in Triadic Concept Analysis and compute triadic generators and association rules, including implications without any need for a preprocessing step to convert the triadic representation into a dyadic one. Our contributions are as follows. First, we adapt the iPred algorithm for precedence link computation in concept lattices to the triadic framework. Then, new algorithms are proposed to compute triadic generators by extending the notion of faces to further calculate association rules. Finally, an empirical study is conducted in order to mainly show the performance of our prototype on triadic contexts and estimate the cost of each one of its components.

Cotesia flavipes Cameron (Hymenoptera: Braconidae) was introduced in Uganda in 1998 for the biological control of the old association cereal stemborer Chilo partellus (Swinhoe) (Lepidoptera: Crambidae). However there is little information on whether this parasitoid will attack new association Lepidoptera, which in turn may have implications on its efficacy on Ch. partellus. This study investigated the incidence of introduced Co. flavipes on Ch. partellus, and new association lepidopteran species and associated effects on its efficacy. Parasitism levels for Co. flavipes in several locations varied between 13.7–34.8% and 1.5–18.8% on Ch. partellus and new association hosts, respectively. Implications for biological control of stemborers in Uganda are discussed.

In order to predict host accessibility by the pupal parasitoid Xanthopimpla stemmator (Thunberg), four grass species (Sorghum bicolor, Pennisetum purpureum, Sorghum arundinaceum and Zea mays) were sampled for stemborer pupae in Kwale, in the low altitudes of southern Kenya, and in Trans-Nzoia, in the high altitudes of western Kenya. The pupal position of Chilo orichalcociliellus (Strand), Chilo partellus (Swinhoe), Sesamia calamistis Hampson, Sesamia sp. nr oriaula (Tams and Bowden) and Busseola fusca (Fuller) in the plant were determined in relation to (a) the distance of pupae from the edge of the stem (depth), (b) the distance between the moth-exit hole and the head of the pupa (location) and (c) the length of the tunnel from the moth-exit hole to the base of the tunnel. Pupal depth and location for C. partellus and B. fusca varied significantly in the different plant species tested, and the pupae tended to be embedded deeper in cultivated than wild hosts. On all host species, the borers were located at a depth less than 0.35 cm. Most C. orichalcociliellus and S. calamistis pupae were found pupating in the ears of maize or the upper part of the wild hosts' stem. Sesamia sp. nr oriaula was only collected from the lower parts of P. purpureum. For B. fusca, tunnel length varied significantly among plant species and was longer in cultivated hosts. Xanthopimpla stemmator has an ovipositor length of about 0.52 cm, thus it is anticipated that the parasitoid could easily reach and parasitize the pupae in these host species.

This study aimed to evaluate the oncological and voice outcomes of transoral laser microsurgery for tumour stage T sub(1b) stage glottic cancer patients. A prospective cohort study in a tertiary care head and neck cancer centre included tumour-node-metastasis stage T sub(1b)N sub(0)M sub(0) glottic cancer patients scheduled to undergo transoral laser microsurgery from January 2002 until June 2014. Kaplan-Meier five-year analyses of local control, overall survival, disease-specific survival and laryngeal preservation were performed. Voice Handicap Index-10 scores and maximum phonation times were also recorded. Twenty-one participants with a mean age of 66.8 years were enrolled. The mean follow up was 56.5 months. Kaplan-Meier 5-year survival analysis illustrated a local control rate of 82 per cent, overall survival of 88 per cent, disease-specific survival of 100 per cent, and laryngeal preservation of 100 per cent. The pre-operative Voice Handicap Index-10 score was 19.1 plus or minus 9.47 (mean plus or minus standard deviation (SD)) and the post-operative scores were 13.5 plus or minus 9.29 at three months, 10.44 plus or minus 9.70 at one year and 5.83 plus or minus 4.91 at two years. The pre-operative maximum phonation time was 16.23 plus or minus 5.46 seconds (mean plus or minus SD) and the post-operative values were 14.44 plus or minus 6.73 seconds at three months, 15.27 plus or minus 5.71 seconds at one year and 14.33 plus or minus 6.44 seconds at two years. Transoral laser microsurgery yields relatively high rates of oncological control and acceptable voice outcomes, and thus shows utility as a primary treatment modality for T sub(1b) glottic cancer.