We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co‐expression networks (CNs) for ...46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver‐specific genes co‐expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver‐specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver‐specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin‐like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.
Synopsis
Integrative network analyses identify liver‐specific drug targets that can be used to effectively treat liver diseases including nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC).
Co‐expression networks are generated for 46 human tissues and liver cancer.
Genes that are co‐expressed with fatty acid synthase (FASN) only in liver tissue are identified.
Inhibition of liver‐specific genes decreases liver fat and cell growth.
Liver‐specific genes can be targeted in order to treat NAFLD and HCC.
Integrative network analyses identify liver‐specific drug targets that can be used to effectively treat liver diseases including nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC).
Abstract
Biological networks provide new opportunities for understanding the cellular biology in both health and disease states. We generated tissue specific integrated networks (INs) for liver, ...muscle and adipose tissues by integrating metabolic, regulatory and protein-protein interaction networks. We also generated human co-expression networks (CNs) for 46 normal tissues and 17 cancers to explore the functional relationships between genes as well as their relationships with biological functions, and investigate the overlap between functional and physical interactions provided by CNs and INs, respectively. These networks can be employed in the analysis of omics data, provide detailed insight into disease mechanisms by identifying the key biological components and eventually can be used in the development of efficient treatment strategies. Moreover, comparative analysis of the networks may allow for the identification of tissue-specific targets that can be used in the development of drugs with the minimum toxic effect to other human tissues. These context-specific INs and CNs are presented in an interactive website http://inetmodels.com without any limitation.
Coriander is one of the most widely used herb. Coriander generally grown for leaf and grain purpose throughout the world. Induction of mutation is considered to be effective in improving various ...characteristics in plants like seed germination, plant vigour, yield etc. In present study we used three different chemical mutagens Colchicine, Sodium azide (SA) and Methyl methane sulphonate (MMS) on four different varieties of coriander (Green wonder, Cross-91, Mrudul and Surabhi). The study was performed by exposing the seeds of four varieties of coriander (Coriandrum sativum L.) to Colchicine (0.01%,0.02%,0.03% and 0.04%), Sodium azide (SA) at (0.1%,0.2%,0.3% and 0.4%) and Methyl methane sulphonate (MMS) at (0.01%,0.02%,0.03% and 0.04%) respectively. The observations were made on seed germination in field and laboratory conditions and the observations on seedling height, number of primary branches and leaves were made in field conditions. All the mutagens significantly affect the germination and seedling growth. The study revealed that germination percentage, plant height, no. of primary branches and leaves decreased with increase in dose/concentration of mutagen. Among three different chemical mutagen we observed that colchicine is better mutagen for induction of mutagen after that sodium azide (SA) had good results for seed treatment. Some of the concentrations of methyl methane sulphonate (MMS) (0.01% & 0.02%) were better. Among all four varieties of coriander Cross-91 gave better result after that Mrudul and Surabhi respond well to some concentrations. We categories the effectiveness of mutagen to induce mutation in coriander as MMS>SA>Colchicine.
Real-world datasets consist of data representations (views) from different sources which often provide information complementary to each other. Multi-view learning algorithms aim at exploiting the ...complementary information present in different views for clustering and classification tasks. Several multi-view clustering methods that aim at partitioning objects into clusters based on multiple representations of the object have been proposed. Almost all of the proposed methods assume that each example appears in all views or at least there is one view containing all examples. In real-world settings this assumption might be too restrictive. Recent work on Partial View Clustering addresses this limitation by proposing a Non-negative Matrix Factorization based approach called PVC. Our work extends the PVC work in two directions. First, the current PVC algorithm is designed specifically for two-view datasets. We extend this algorithm for the k partial-view scenario. Second, we extend our k partial-view algorithm to include view specific graph laplacian regularization. This enables the proposed algorithm to exploit the intrinsic geometry of the data distribution in each view. The proposed method, which is referred to as GPMVC (Graph Regularized Partial Multi-View Clustering), is compared against 7 baseline methods (including PVC) on 5 publicly available text and image datasets. In all settings the proposed GPMVC method outperforms all baselines. For the purpose of reproducibility, we provide access to our code.
Tardive Dyskinesia is a severe side effect of chronic neuroleptic treatment consisting of abnormal involuntary movements, characterized by orofacial dyskinesia. The study was designed to investigate ...the protective effect of lycopene against haloperidol induced orofacial dyskinesia possibly by neurochemical and neuroinflammatory modulation in rats. Rats were administered with haloperidol (1mg/kg, i.p for 21 days) to induce orofacial dyskinesia. Lycopene (5 and 10mg/kg, p.o) was given daily 1hour before haloperidol treatment for 21 days. Behavioral observations (vacuous chewing movements, tongue protrusions, facial jerking, rotarod activity, grip strength, narrow beam walking) were assessed on 0th, 7th, 14th, 21st day after haloperidol treatment. On 22nd day, animals were killed and striatum was excised for estimation of biochemical parameters (malondialdehyde, nitrite and endogenous enzyme (GSH), pro-inflammatory cytokines Tumor necrosis factor, Interleukin 1β, Interleukin 6 and neurotransmitters level (dopamine, serotonin, nor epinephrine, 5-Hydroxyindole acetic acid (5-HIAA), Homovanillic acid, 3,4- dihydroxyphenylacetic acid. Haloperidol treatment for 21 days impaired muscle co-ordination, motor activity and grip strength with an increased in orofacial dyskinetic movements. Further free radical generation increases MDA and nitrite levels, decreasing GSH levels in striatum. Neuroinflammatory markers were significantly increased with decrease in neurotransmitters levels. Lycopene (5 and 10mg/kg, p.o) treatment along with haloperidol significantly attenuated impairment in behavioral, biochemical, neurochemical and neuroinflammatory markers. Results of the present study attributed the therapeutic potential of lycopene in the treatment (prevented or delayed) of typical antipsychotic induced orofacial dyskinesia.
MicroRNAs (miRNAs/miRs) represent a novel class of small non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with complementary sequences in the 3' untranslated ...region (UTR) of target mRNAs. Functional studies suggest that miRNAs control almost every biological process, and their aberrant expression leads to a disease state, such as cancer. Differential expression of miRNAs in cancerous versus normal cells have generated enormous interest for the development of miRNA-based cancer cell-targeted therapeutics. Depending on the miRNA function and expression in cancer, two types of miRNA-based therapeutic strategies can be utilized that either restore or inhibit miRNA function through exogenous delivery of miRNAs mimics or inhibitors (anti-miRs). However, hydrophilic nature of miRNA mimics/anti-miRs, sensitivity to nuclease degradation in serum, poor penetration and reduced uptake by the tumor cells are chief hurdles in accomplishing their efficient in vivo delivery. To overcome these barriers, several nanotechnology-based systems are being developed and tested for delivery efficacy. This review summarizes the importance of miRNAs-based therapeutics in cancer, associated translational challenges and novel nanotechnology-assisted delivery systems that hold potential for next-generation miRNA-based cancer therapeutics.
Abstract Sunscreen formulations containing UVB filters, such as Zinc-oxide (ZnO) and titanium-dioxide (TiO2) nanoparticles (NPs) have been developed to limit the exposure of human skin to ...UV-radiations. Unfortunately, these UVB protective agents have failed in controlling the skin cancer incidence. We recently demonstrated that silver nanoparticles (Ag-NPs) could serve as novel protective agents against UVB-radiations. Here our goal was to perform comparative analysis of direct and indirect UVB-protection efficacy of ZnO-, TiO2 - and Ag-NPs. Sun-protection-factor calculated based on their UVB-reflective/absorption abilities was the highest for TiO2 -NPs followed by Ag- and ZnO-NPs. This was further confirmed by studying indirect protection of UVB radiation-induced death of HaCaT cells. However, only Ag-NPs were active in protecting HaCaT cells against direct UVB-induced DNA-damage by repairing bulky-DNA lesions through nucleotide-excision-repair mechanism. Moreover, Ag-NPs were also effective in protecting HaCaT cells from UVB-induced oxidative DNA damage by enhancing SOD/CAT/GPx activity. In contrast, ZnO- and TiO2 -NPs not only failed in providing any direct protection from DNA-damage, but rather enhanced oxidative DNA-damage by increasing ROS production. Together, these findings raise concerns about safety of ZnO- and TiO2-NPs and establish superior protective efficacy of Ag-NPs.
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