Cell specific apoptosis by RLX is mediated by NFκB in human colon carcinoma HCT-116 cells

BACKGROUND: Resistance to chemotherapy represents a major obstacle in correcting colorectal carcinomas (CRC). Inspite of recent advances in the treatment of metastatic disease, the prognosis of the patients remains poor. RLX, a vasicinone analogue has been reported to possess potent bronchodilator, anti-asthmatic and anti-inflammatory properties. However, its anti-cancer activity is unknown. RESULTS: Here, we report for the first time that RLX has anti-cancer property against panel of human cancer cell lines and most potent activity was found against HCT-116 cells with IC(50) value of 12 μM and have further investigated the involvement of NFκB and caspase-3 in RLX action in CRC apoptosis. Following RLX and BEZ-235 treatment in HCT-116, we observed significant down-regulation of NFκB (1 to 0.1 fold) and up-regulation of caspase-3 (1 to 2 fold) protein expressions. Additionally, morphological studies revealed membrane blebbing, cell shrinkage, chromatin condensation and finally apoptosis in HCT-116 cells. CONCLUSIONS: Overall, these findings indicate that RLX is a potent small molecule which triggers apoptosis, and promising potential candidate to be a chemotherapeutic agent

Transcriptomic landscape of lncRNAs in inflammatory bowel disease

BACKGROUND: Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn’s disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD. METHODS: In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in 96 colon pinch biopsies (inflamed and non-inflamed) extracted from multiple colonic locations from 45 patients (CD = 13, UC = 20, controls = 12) using an expression microarray platform. RESULTS: In our study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In cases of inflamed CD and UC, we identified 438 and 745 differentially expressed lncRNAs, respectively, while in cases of the non-inflamed CD and UC, we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment (P-value <0.001, Pearson’s Chi-squared test) for 96 differentially expressed lncRNAs and 154 protein-coding genes within the IBD susceptibility loci. Furthermore, we found strong positive expression correlations for the intersecting and cis-neighboring differentially expressed IBD loci-associated lncRNA-protein-coding gene pairs. The functional annotation analysis of differentially expressed genes revealed their involvement in the immune response, pro-inflammatory cytokine activity and MHC protein complex. CONCLUSIONS: The lncRNA expression profiling in both inflamed and non-inflamed CD and UC successfully stratified IBD patients from the healthy controls. Taken together, the identified lncRNA transcriptional signature along with clinically relevant parameters suggest their potential as biomarkers in IBD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0162-2) contains supplementary material, which is available to authorized users

The identification and functional annotation of RNA structures conserved in vertebrates

Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human–mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality.</jats:p

Order in stress - Lessons from the inanimate world

Life can be considered as an outcome of complex molecular processes which result in the existence of a thermodynamically ordered, far from equilibrium state. The maintenance of this order in living systems is energy-dependent and follows the basic laws of physics and chemistry. However, at times of stress, when the energy pool of a cell goes down, maintaining dynamic order becomes difficult. In such a situation, how can the equilibrium imposed by the second law of thermodynamics be avoided? Can there be order in stress (Minsky et al 2002)

Cellular AATF gene encodes a novel miRNA that can contribute to HIV-1 latency

237-240HIV-1 encoded microRNA hiv1-miR-H1 is known to induce CD4+ lymphopenia through its ability to downregulate cellular AATF gene. The present study directed to examine the target sites of this miRNA on AATF gene revealed the existence of a novel miRNA designated as hmiR-che-1 which had the inherent capacity to target HIV-1 genome especially regions coding for hiv1-miR-H1 as well as Vpr gene. Further, the expression of AATF gene coupled with its encoded microRNA hmiR-che-1 exhibited characteristic antagonism with the expression of hiv1-miR-H1 within the lymphocytes, derived from asymptomatic as well as symptomatic AIDS subjects. Based upon these observations, we propose that the widely recognised HIV-1 latency in CD4+ T-lymphocytes may arise, because of the orchestrated balance that may exist between the expression levels of hiv1-miR-H1 and hmiR-che-1 within lymphocytes infected with HIV-

ANTIDERMATOPHYTIC ACTIVITY OF ANGIOSPERMIC PLANTS: A REVIEW

In recent years, there has been increasing interest worldwide in the use of alternative/herbal medicine for the prevention and treatment of fungaldiseases. Currently, however, quality-related problems (lack of consistency, safety, and efficacy) seem to be overshadowing the potential genuinebenefits of various herbal products for the treatment of fungal diseases. Extracts obtained from many plants have recently gained a great popularityand scientific interest. Since the middle ages, natural plant preparations have been widely used for treatment of fungal diseases. Treatment of thefungal pathogen is becoming increasingly difficult due to antifungal drug resistance, especially with fluconazole, which is a commonly used azole.This paper reviews the in vitro activity of angiospermic plant extracts and their major compounds against dermatophytes and also a compilation ofupdated information on angiospermic plant extracts with antifungal properties.Keywords: Dermatophytes, Extracts, Medicinal plants

Anthocyanidins-enriched bilberry extracts inhibit 3T3-L1 adipocyte differentiation via the insulin pathway

Abstract Background Obesity and metabolic syndrome are important public concerns, and there is increasing demand for effective therapeutic strategies. Flavonoids are expected to improve the risk factors associated with metabolic syndrome. Anthocyanidins are a kind of flavonoids; well known for their anti-oxidative, anti-inflammatory and anti-tumor properties. However, their effects on adipocytes and molecular systems are not well defined. In this study, we examined the effects of anthocyanidins-enriched bilberry extracts on adipocyte differentiation. Methods Utilizing 3T3-L1 cell line, we investigated that bilberry extracts and anthocyanidins induced inhibition of lipid accumulation during adipogenesis. To identify what is the most important bilberry mediated-effect, we analyzed the expressions of key transcriptional factors associated with adipocyte differentiation by Real Time (RT)-PCR. From the results of RT-PCR, we hypothesized that bilberry extracts and anthocyanidins blocks insulin signal, we determined the phosphorylation of tyrosine residues of insulin receptor substrate 1 (IRS1) protein by western blotting analysis. In addition, we compared the whole-genome expression profiles of early stage of adipocyte differentiation under four different growth conditions (DMSO, bilberry, two anthocyanidins) by microarray analyses and Gene Set Enrichment Analysis (GSEA). Results Exposure to bilberry extracts and anthocyanidins during adipocyte differentiation inhibited 3T3-L1 differentiation. During this period, bilberry extracts and anthocyanidin significantly decreased a key adipocyte differentiation-associated marker, peroxisome proliferator-activated receptor- γ (Ppar γ ) and sterol regulatory element-binding protein 1c (Srebp1c). Western blotting analysis showed that bilberry extracts and anthocyanidin decreased the phosphorylation of tyrosine residues of IRS1. In addition, microarray experiments and GSEA data revealed significantly altered expression of the known genes of the insulin pathway in cells treated with bilberry extracts or anthocyanidins in the early differentiation stages. Conclusions Our data demonstrate that anthocyanidin enriched bilberry extracts strongly inhibit the adipocyte differentiation via the insulin pathway. Furthermore, bilberry extracts might be used as a potential complementary treatment for the obese patients with metabolic syndrome.</p

Maggot Therapy and its Implications in Veterinary Medicine: An Overview

Alternative therapies to conventional wound management are available now-a-days to facilitate faster wound healing without any complications. Among various alternative therapies, it has been well established that maggot therapy can be used successfully to treat chronic long-standing infected wounds which previously failed to respond to conventional treatment. Maggot therapy employs the use of freshly emerged, sterile larvae of the common greenbottle fly, Phaenicia (Lucilia) sericata, and is a form of artificially induced myiasis in a controlled clinical situation. Maggot therapy, however, is used relatively little in veterinary medicine. Nevertheless, concern over antibiotic resistance and the increase in demand for organic husbandry and residue-free meat and milk, suggest that it is an option which merits further consideration. In this review article, authors’ discuss the role of maggots and their preparation for veterinary medical use