Methylomic analysis identifies C11orf87 as a novel epigenetic biomarker for GI cancers.

Gastric cancer is one of the leading causes of cancer death worldwide. Previous studies demonstrated that activation of STAT3 is crucial for the development and progression of gastric cancer. However, the role of STAT3 in neuronal related gene methylation in gastric cancer has never been explored. In this study, by using DNA methylation microarray, we identified a potential STAT3 target, C11orf87, showing promoter hypomethylation in gastric cancer patients with lower STAT3 activation and AGS gastric cancer cell lines depleted with STAT3 activation. Although C11orf87 methylation is independent of its expression, ectopic expression of a constitutive activated STAT3 mutant upregulated its expression in gastric cancer cell line. Further bisulfite pyrosequencing demonstrated a progressive increase in DNA methylation of this target in patient tissues from gastritis, intestinal metaplasia, to gastric cancer. Intriguingly, patients with higher C11orf87 methylation was associated with better survival. Furthermore, hypermethylation of C11orf87 was also frequently observed in other GI cancers, as compared to their adjacent normal tissues. These results suggested that C11orf87 methylation may serve as a biomarker for diagnosis and prognosis of GI cancers, including gastric cancer. We further postulated that constitutive activation of STAT3 might be able to epigenetically silence C11orf87 as a possible negative feedback mechanism to protect the cells from the overactivation of STAT3. Targeted inhibition of STAT3 may not be appropriate in gastric cancer patients with promoter hypermethylation of C11orf87.

Prevalence and antibiogram of coagulase negative Staphylococci in bioaerosols from different indoors of a university in India.

BACKGROUND: Staphylococci species are the major constituents of infectious bioaerosols, particularly methicillin-resistant Staphylococci (MRS) have serious health impacts. Here, the bacterial burden was quantified, especially prevalence of MRS in bioaerosols collected from indoors of Dr. B.R. Ambedkar Central Library (DBRACL) and Central Laboratory Animal Resources (CLAR) of Jawaharlal Nehru University, New Delhi, India. Air samplings from DBRACL and CLAR were done using the settle plate method and SKC biosampler, respectively. RESULTS: This study showed a maximum 6757 CFU/m2/hr of bacterial load in the DBRACL reading room, while unacceptable bacterial loads (> 1000 CFU/m3 of air) at different sites of CLAR. Further, at both the sampling sites the predominance of coagulase negative Staphylococci (CNS) was observed. A total 22 and 35 Staphylococci isolates were isolated from DBRACL and CLAR bioaerosols, respectively. Majority (16/22) of the Staphylococcal isolates from DBRACL belonged to human-associated Staphylococci where S. haemolyticus (5/22) was the most dominating species. However, in CLAR facility centre, animal-associated Staphylococci (19/35) were dominating, where S. xylosus (12/35) was the most dominating species. Further, antibiotic sensitivity tests revealed 41% MRS and 73% multidrug resistant (MDR) among airborne Staphylococci from DBRACL indoor bioaerosols. Similarly, in CLAR facility, approximately, 66% Staphylococci isolates were methicillin resistant, out of which 2 isolates showed high MIC value ≥ 16 µg/mL. Further, we confirmed the presence of 49% multidrug resistant Staphylococci in the indoor air of CLAR facility. CONCLUSIONS: This study suggested that the exposure of workers and students in CLAR to such a high concentration of drug-resistant Staphylococci should not be undermined, as these bacterial concentrations are the direct representative of inhalable particulate matter (PM2.5) as per collection procedure. Simultaneously, passive sampling from DBRACL assessed the risks due to microbial contamination in particle agglomerates, which may deposit on the crucial surfaces such as wounds/ cuts or on the frequently used items.

Review on the Role of Epigenetic Modifications in Doxorubicin-Induced Cardiotoxicity.

Use of anthracyclines such as doxorubicin (DOX), for the treatment of cancer, is known to induce cardiotoxicity, begetting numerous evaluations of this adverse effect. This review emphasizes the mechanism of how consideration of DOX-induced cardiotoxicity is important for the development of cardioprotective agents. As DOX is involved in mitochondrial dysfunction, enzymes involved in epigenetic modifications that use mitochondrial metabolite as substrate are most likely to be affected. Therefore, this review article focuses on the fact that epigenetic modifications, namely, DNA methylation, histone modifications, and noncoding RNA expression, contribute to DOX-associated cardiotoxicity. Early interventions needed for patients undergoing chemotherapy, to treat or prevent heart failure, would, overall, improve the survival, and quality of life of cancer patients. These epigenetic modifications can either be used as molecular markers for cancer prognosis or represent molecular targets to attenuate DOX-induced cardiotoxicity in cancer patients.

Bactericidal activity of curcumin I is associated with damaging of bacterial membrane.

Curcumin, an important constituent of turmeric, is known for various biological activities, primarily due to its antioxidant mechanism. The present study focused on the antibacterial activity of curcumin I, a significant component of commercial curcumin, against four genera of bacteria, including those that are Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa). These represent prominent human pathogens, particularly in hospital settings. Our study shows the strong antibacterial potential of curcumin I against all the tested bacteria from Gram-positive as well as Gram-negative groups. The integrity of the bacterial membrane was checked using two differential permeabilization indicating fluorescent probes, namely, propidium iodide and calcein. Both the membrane permeabilization assays confirmed membrane leakage in Gram-negative and Gram-positive bacteria on exposure to curcumin I. In addition, scanning electron microscopy and fluorescence microscopy were employed to confirm the membrane damages in bacterial cells on exposure to curcumin I. The present study confirms the broad-spectrum antibacterial nature of curcumin I, and its membrane damaging property. Findings from this study could provide impetus for further research on curcumin I regarding its antibiotic potential against rapidly emerging bacterial pathogens.