Perspective Chapter: Epigenetic Therapy - The Future Treatment for Cancer

Scientists have made a remarkable breakthrough by uncovering DNA and its role in living organisms. Epigenetics examines the phenotypic divergences due to DNA methylation and its effects at certain genetic spots. Epigenetic and genetic problems combine to cause cancer and its growth, as seen by frequent mutations in genes that manage the epigenome. Recently, new therapies targeting epigenetic alterations have been proposed. Drugs with longer shelf life and better absorption are also being manufactured and tested. On this aspect, CRISPR technology has been used to create various strategies for epigenetic engineering and is a practical approach to understanding and manipulating biological processes. Furthermore, studies on the advantages of probiotics have advanced previous interventional studies to recognize the molecular mechanisms involved. Numerous probiotic genomes include epigenetic components that influence gene expression for fundamental functions. Consequently, we suggest investigations incorporating genomic and meta-epigenomic information to better understand the mode of action of probiotics and their related microbiomes in epigenetic therapy. Here, we review established epigenetic discoveries, combined with the rapid advancement of immunotherapies, to create new possibilities for cancer treatment

SRF is required for maintenance of astrocytes in non-reactive state in the mammalian brain

Astrocytes play several critical roles in the normal functioning of the mammalian brain, including ion homeostasis, synapse formation, and synaptic plasticity. Following injury and infection or in the setting of neurodegeneration, astrocytes become hypertrophic and reactive, a process termed astrogliosis. Although acute reactive gliosis is beneficial in limiting further tissue damage, chronic gliosis becomes detrimental for neuronal recovery and regeneration. Several extracellular factors have been identified that generate reactive astrocytes; however, very little is known about the cell-autonomous transcriptional mechanisms that regulate the maintenance of astrocytes in the normal non-reactive state. Here, we show that conditional deletion of the stimulus-dependent transcription factor, serum response factor (SRF) in astrocytes

SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration

Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. Thes

Conjugal transfer of erm(B) and multiple tet genes from Lactobacillus spp. to bacterial pathogens in animal gut, in vitro and during food fermentation

Three strains of Lactobacillus comprising Lactobacillus salivarius (CHS-1E and CH7-1E) and Lactobacillus reuteri (CH2-2) previously isolated from chicken meat were analyzed for their transferability of antibiotic resistance (AR) genes to pathogenic strains under in vivo, in vitro, and during food fermentation. For in vivo model, Albino Wistar rats were inoculated with 10(10) CFU/g/ml of Enterococcus faecalis JH2-2 (recipient). After 7 days, either of two donors L. salivarius CH7-1E or L. reuteri harbouring erythromycin and tetracycline resistance genes] were introduced at a concentration of 10(9) CFU/ml daily for 1 week. Two days after donor introduction, there was a stable increase in the number of transconjugants in the animal faeces from 10(2) to 10(3)CFU/g and presented erm (B), tet(M), tet(L) and tet(W) in their genome like donor strains. Similar observations were made with in vitro filter mating between CHS-1E, CH2-2 and CH7-1E and E. faecalis JH2-2 with transfer frequencies of 1 x 10(-4), 3.8 x 10(-3) and 2 x 10(-3) per donor cell respectively. With the results obtained in vivo and in vitro, the AR transferability of donor strains was estimated during food fermentation (chicken sausage, fermented milk or idii batter) with pathogenic recipient strains added as contaminants. At the end of mating period, phenotypic resistance to erythromycin and tetracycline in Listeria monocytogenes and Yersinia enterocolitica strains was observed. This study showed the ability of food borne Lactobacillus in diffusing their AR traits in diverse natural environments increasing their concern of AR dissemination in the food chain when used as food additives and/or probiotics

Heterogeneity of macrolide-lincosamide-streptogramin phenotype & conjugal transfer of erm(B) in Pediococcus pentosaceus

Background & objectives: Pediococcus pentosaceus has been reported to cause clinical infections while it is being promoted as probiotic in food formulations. Antibiotic resistance (AR) genes in this species are a matter of concern for treating clinical infections. The present study was aimed at understanding the phenotypic resistance of P. pentosaceus to macrolide-lincosamide-streptogramin B (MLSB) antibiotics and the transfer of AR to pathogens. Methods: P. pentosacues isolates (n=15) recovered from fermented foods were screened for phenotypic resistance to MLSB antibiotics using disc diffusion and microbroth dilution methods. Localization and transferability of the identified resistance genes, erm(B) and msr(C) were evaluated through Southern hybridization and in vitro conjugation methods. Results: Four different phenotypes; sensitive (S) (n=5), macrolide (M) (n=7), lincosamide (L) (n=2) and constitutive (cMLS(B)) (n=1) were observed among the 15 P. pentosaceus isolates. High-level resistance (>256 mu g/ml) to MLSB was observed with one cMLS(B) phenotypic isolate IB6-2A. Intermediate resistance (8-16 mu g/ml) to macrolides and lincosamides was observed among M and L phenotype isolates, respectively. Cultures with S phenotype were susceptible to all other antibiotics but showed unusual minimum inhibitory concentration (MIC) values of 8-16 mu g/ml for azithromycin. Southern hybridization studies revealed that resistance genes localized on the plasmids could be conjugally transferred to Enterococcus faecalis JH2-2. Interpretation & conclusions: The study provides insights into the emerging novel resistance patterns in P. pentosaceus and their ability to disseminate AR. Monitoring their resistance phenotypes before use of MLS antibiotics can help in successful treatment of Pediococcal infections in humans