With the growing advent of nanotechnology in medicine (therapeutic, diagnostic and imaging applications), cosmetics, electronics, clothing and food industries, exposure to nanomaterials (NMs) is on the rise and therefore exploring their toxic biological effects have gained great significance. In vitro and in vivo studies over the last decade have revealed that NMs have the potential to cause cytotoxicity and genotoxicity although some contradictory reports exist. However, there are only few studies which have explored the epigenetic mechanisms (changes to DNA methylation, histone modification and miRNA expression) of NM-induced toxicity, and there is a scarcity of information and many questions in this area remain unexplored and unaddressed. This review comprehensively describes the epigenetic mechanisms involved in the induction of toxicity of engineered NMs, and provides comparisons between similar effects observed upon exposure to small or nanometer-sized particles. Lastly, gaps in existing literature and scope for future studies that improve our understanding of NM-induced epigenetic toxicity are discussed.

BackgroundY-box binding protein-1 is an evolutionary conserved transcription and translation regulating protein that is overexpressed in various human malignancies, including breast cancer. Despite reports of YB-1 and its association with distant spread of breast cancer, the intrinsic mechanism underlying this observation remains elusive. This study investigates the role of YB-1 in mediating metastasis in highly invasive breast cancer cell lines.MethodsSilencing the YBX1 gene (which encodes the YB-1 protein) by small interfering RNA (siRNA) was performed in MDA-MB-231 and Hs578T breast cancer cell lines, followed by phenotypic assays including cell migration and invasion assays. Gene expression profiling using Affymetrix GeneChip® Human Transcriptome 2.0 array was subsequently carried out in YB-1 silenced MDA-MB-231 cells. Overexpression and silencing of YBX1 were performed to assess the expression of CORO1C, one of the differentially regulated genes from the transcriptomic analysis. A Gaussia luciferase reporter assay was used to determine if CORO1C is a putative YB-1 downstream target. siRNA-mediated silencing of CORO1C and down-regulation of YBX1 in CORO1C overexpressing MDA-MB-231 cells were performed to evaluate cell migration and invasion.ResultsDownregulation of the YB-1 protein inhibited cell migration and invasion in MDA-MB-231 breast cancer cells. Global gene expression profiling in the YBX1 silenced MDA-MB-231 cells identified differential expression of several genes, including CORO1C (which encodes for an actin binding protein, coronin-1C) as a potential downstream target of YB-1. While knockdown of YBX1 gene decreased CORO1C gene expression, the opposite effects were seen in YB-1 overexpressing cells. Subsequent verification using the reporter assay revealed that CORO1C is an indirect downstream target of YB-1. Silencing of CORO1C by siRNA in MDA-MB-231 cells was also observed to reduce cell migration and invasion. Silencing of YBX1 caused a similar reduction in CORO1C expression, concomitant with a significant decrease in migration in Hs578T cells. In coronin-1C overexpressing MDA-MB-231 cells, increased migration and invasion were abrogated by YB-1 knockdown.ConclusionIt would appear that YB-1 could regulate cell invasion and migration via downregulation of its indirect target coronin-1C. The association between YB-1 and coronin-1C offers a novel approach by which metastasis of breast cancer cells could be targeted and abrogated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3187-7) contains supplementary material, which is available to authorized users.

BackgroundMaternal diabetes alters gene expression leading to neural tube defects (NTDs) in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs) to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development.Methods and FindingsNSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation) and global DNA methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin) and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1) proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p) predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers.Conclusion/InterpretationThis study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy.

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Despite advances in treatment, the highly metastatic nature of breast tumors has given rise to the urgent need for development of novel therapeutic and prognostic markers. miR-93 is known to regulate the epithelial to mesenchymal transition process and to influence metastatic spread in breast carcinoma, although the exact mechanism(s)/genes involved remain unknown. In the present study, we examined the role of miR-93 in MDA-MB-231 breast cancer cells. Overexpression of mature miR-93-5p in MDA-MB-231 cells decreased cell migratory capability and invasive potential, as well as increased adhesion. In contrast, inhibition of miR-93 induced the opposite effects. miRNA-mRNA target prediction (TargetScan) identified WNK lysine deficient protein kinase 1 (WNK1), which is known to interact with diverse signaling pathways and regulate cell proliferation, survival, angiogenesis and metastasis, as one of the potential targets of miR-93. Furthermore, we showed by luciferase assay that WNK1 is a putative miR-93 target. siRNA mediated silencing of WNK1 also decreased the invasive ability of the cells, suggesting that the effects of miR-93 may be attributed at least in part to decreased WNK1 expression. Further in vivo studies are required to ascertain the miR-93-WNK1-metastasis cascade, that has potential implications in breast cancer therapy.

Chronic activation of microglia is the hallmark of numerous neuropathologies such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. The activated microglia perpetuate inflammation by releasing an array of pro-inflammatory and neurotoxic factors, which eventually exacerbate neurotoxicity and neurodegeneration upon chronic activation of these cells. However, under acute conditions, activated microglia elicit pro-inflammatory as well as anti-inflammatory responses that are associated with neuroprotection. Given the role of microglia in neuroinflammation, recent studies have attempted to unravel the mechanisms that aid to establish microglial cell-based therapy. Areas covered: While total suppression of microglial activation may compromise its beneficial role in tissue repair in the aftermath of an insult, the benefits of modulating microglial activation and promoting microglia polarization to a neuroprotective phenotype have been highlighted recently. Expert opinion: So far, the therapeutic strategy focussed on neutralizing microglia-mediated neuroinflammation using drugs that block the release of pro-inflammatory mediators has limitations, such as unwarranted side effects. Recent advances reveal several alternative molecular targets and potential epi-drugs that are capable of modulating microglial function and promoting neuroprotection. This review discusses the recent progress made in understanding the mechanisms of microglia-mediated neuroinflammation in various neuropathologies, and the emerging anti-inflammatory therapeutic strategies in this field.

INTRODUCTION:Chronic osteomyelitis (COM) is a common infection, especially in developing countries. An adequate bone biopsy specimen processed with appropriate microbiology culture methods for isolation and identification of the causative organisms is considered as the gold standard for the diagnosis of osteomyelitis.MATERIALS AND METHODS:The present study is a retrospective microbiology analysis of the specimen from 219 clinically diagnosed cases of COM between January 2013 and April 2016.RESULTS:The overall culture positivity was 111/219 (50. 6%), colonization was seen in 22/219 (10.5%), while the rest 86/219 (39.3%) were culture-negative specimen; culture positivity was highest from tissue specimen (71/113, 62.8%). Among the swabs, 40/106 (37.7%) were culture positive. About 28/40 (70%) culture-positive swabs showed significant growth of Gram-positive organisms. Colonization with skin flora such as diphtheroids and Coagulase-negative Staphylococci was seen in 22/106 (20.7%) of the swabs. Sterile cultures (44/106, 41.6%) were high among the swab specimen. Gram-positives were most common (75/111, 67.56%). Staphylococcus aureus was the predominant organism isolated in 70/111 (63%) cases. Gram-negative bacilli showed a high level of antibiotic resistance.CONCLUSION:As per our data, the culture yield from wound swabs was low or contaminated with normal skin flora, as compared to the biopsy or tissue specimen. Hence, an appropriate sampling of the infected bone using recommended protocols is highly essential for improving microbiological yield and the outcome of COM.

Apophysomyces elegans species complex is an important cause of cutaneous mucormycosis in India. However, majority of those cases are reported as case reports only. We desired to analyze our patients with Apophysomyces infection reported over 25 years (1992–2017) to understand the epidemiology, management, and outcome of the disease. During the study period 24 cases were reported, and the majority (95.8%) of them presented with necrotizing fasciitis following accidental/surgical/iatrogenic trauma. One patient presented with continuous ambulatory peritoneal dialysis (CAPD) related peritonitis. Healthcare related Apophysomyces infection was noted in 29.2% patients. In addition to trauma, comorbidities were noted in 37.5% patients (type 2diabetes mellitus-6, chronic alcoholism-2, and chronic kidney disease-1). Of the 24 isolates, 11 isolates starting from year 2014 were identified as Apophysomyces variabilis by molecular methods. Majority (95.8%) of the patients were managed surgically with or without amphotericin B deoxycholate therapy, while one patient was treated with amphotericin B deoxycholate alone. Among 24 patients, seven (29.1%) recovered, six (25%) patients could not afford antifungal management and left the hospital against medical advice, and 11 (45.9%) patients died.The present case series highlights that necrotizing fasciitis caused by A. variabilis is prevalent in India, and the disease may be healthcare related. Although diagnosis is not difficult, awareness among surgeons is still limited about the infection, leading to a delay in sending samples to the mycology laboratory. Apophysomyces infection must be considered in the differential diagnosis in apatient with progressive necrosis of a wound who is not responding to antibacterial therapy.